@article {1237, title = {Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.}, journal = {Nat Genet}, volume = {42}, year = {2010}, month = {2010 Nov}, pages = {937-48}, abstract = {

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and \~{} 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 {\texttimes} 10$^{-}$$^{8}$), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

}, keywords = {Body Height, Body Mass Index, Body Size, Body Weight, Chromosome Mapping, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Obesity, Polymorphism, Single Nucleotide}, issn = {1546-1718}, doi = {10.1038/ng.686}, author = {Speliotes, Elizabeth K and Willer, Cristen J and Berndt, Sonja I and Monda, Keri L and Thorleifsson, Gudmar and Jackson, Anne U and Lango Allen, Hana and Lindgren, Cecilia M and Luan, Jian{\textquoteright}an and M{\"a}gi, Reedik and Randall, Joshua C and Vedantam, Sailaja and Winkler, Thomas W and Qi, Lu and Workalemahu, Tsegaselassie and Heid, Iris M and Steinthorsdottir, Valgerdur and Stringham, Heather M and Weedon, Michael N and Wheeler, Eleanor and Wood, Andrew R and Ferreira, Teresa and Weyant, Robert J and Segr{\`e}, Ayellet V and Estrada, Karol and Liang, Liming and Nemesh, James and Park, Ju-Hyun and Gustafsson, Stefan and Kilpel{\"a}inen, Tuomas O and Yang, Jian and Bouatia-Naji, Nabila and Esko, T{\~o}nu and Feitosa, Mary F and Kutalik, Zolt{\'a}n and Mangino, Massimo and Raychaudhuri, Soumya and Scherag, Andre and Smith, Albert Vernon and Welch, Ryan and Zhao, Jing Hua and Aben, Katja K and Absher, Devin M and Amin, Najaf and Dixon, Anna L and Fisher, Eva and Glazer, Nicole L and Goddard, Michael E and Heard-Costa, Nancy L and Hoesel, Volker and Hottenga, Jouke-Jan and Johansson, Asa and Johnson, Toby and Ketkar, Shamika and Lamina, Claudia and Li, Shengxu and Moffatt, Miriam F and Myers, Richard H and Narisu, Narisu and Perry, John R B and Peters, Marjolein J and Preuss, Michael and Ripatti, Samuli and Rivadeneira, Fernando and Sandholt, Camilla and Scott, Laura J and Timpson, Nicholas J and Tyrer, Jonathan P and van Wingerden, Sophie and Watanabe, Richard M and White, Charles C and Wiklund, Fredrik and Barlassina, Christina and Chasman, Daniel I and Cooper, Matthew N and Jansson, John-Olov and Lawrence, Robert W and Pellikka, Niina and Prokopenko, Inga and Shi, Jianxin and Thiering, Elisabeth and Alavere, Helene and Alibrandi, Maria T S and Almgren, Peter and Arnold, Alice M and Aspelund, Thor and Atwood, Larry D and Balkau, Beverley and Balmforth, Anthony J and Bennett, Amanda J and Ben-Shlomo, Yoav and Bergman, Richard N and Bergmann, Sven and Biebermann, Heike and Blakemore, Alexandra I F and Boes, Tanja and Bonnycastle, Lori L and Bornstein, Stefan R and Brown, Morris J and Buchanan, Thomas A and Busonero, Fabio and Campbell, Harry and Cappuccio, Francesco P and Cavalcanti-Proen{\c c}a, Christine and Chen, Yii-Der Ida and Chen, Chih-Mei and Chines, Peter S and Clarke, Robert and Coin, Lachlan and Connell, John and Day, Ian N M and den Heijer, Martin and Duan, Jubao and Ebrahim, Shah and Elliott, Paul and Elosua, Roberto and Eiriksdottir, Gudny and Erdos, Michael R and Eriksson, Johan G and Facheris, Maurizio F and Felix, Stephan B and Fischer-Posovszky, Pamela and Folsom, Aaron R and Friedrich, Nele and Freimer, Nelson B and Fu, Mao and Gaget, Stefan and Gejman, Pablo V and Geus, Eco J C and Gieger, Christian and Gjesing, Anette P and Goel, Anuj and Goyette, Philippe and Grallert, Harald and Gr{\"a}ssler, J{\"u}rgen and Greenawalt, Danielle M and Groves, Christopher J and Gudnason, Vilmundur and Guiducci, Candace and Hartikainen, Anna-Liisa and Hassanali, Neelam and Hall, Alistair S and Havulinna, Aki S and Hayward, Caroline and Heath, Andrew C and Hengstenberg, Christian and Hicks, Andrew A and Hinney, Anke and Hofman, Albert and Homuth, Georg and Hui, Jennie and Igl, Wilmar and Iribarren, Carlos and Isomaa, Bo and Jacobs, Kevin B and Jarick, Ivonne and Jewell, Elizabeth and John, Ulrich and J{\o}rgensen, Torben and Jousilahti, Pekka and Jula, Antti and Kaakinen, Marika and Kajantie, Eero and Kaplan, Lee M and Kathiresan, Sekar and Kettunen, Johannes and Kinnunen, Leena and Knowles, Joshua W and Kolcic, Ivana and K{\"o}nig, Inke R and Koskinen, Seppo and Kovacs, Peter and Kuusisto, Johanna and Kraft, Peter and Kval{\o}y, Kirsti and Laitinen, Jaana and Lantieri, Olivier and Lanzani, Chiara and Launer, Lenore J and Lecoeur, C{\'e}cile and Lehtim{\"a}ki, Terho and Lettre, Guillaume and Liu, Jianjun and Lokki, Marja-Liisa and Lorentzon, Mattias and Luben, Robert N and Ludwig, Barbara and Manunta, Paolo and Marek, Diana and Marre, Michel and Martin, Nicholas G and McArdle, Wendy L and McCarthy, Anne and McKnight, Barbara and Meitinger, Thomas and Melander, Olle and Meyre, David and Midthjell, Kristian and Montgomery, Grant W and Morken, Mario A and Morris, Andrew P and Mulic, Rosanda and Ngwa, Julius S and Nelis, Mari and Neville, Matt J and Nyholt, Dale R and O{\textquoteright}Donnell, Christopher J and O{\textquoteright}Rahilly, Stephen and Ong, Ken K and Oostra, Ben and Par{\'e}, Guillaume and Parker, Alex N and Perola, Markus and Pichler, Irene and Pietil{\"a}inen, Kirsi H and Platou, Carl G P and Polasek, Ozren and Pouta, Anneli and Rafelt, Suzanne and Raitakari, Olli and Rayner, Nigel W and Ridderstr{\r a}le, Martin and Rief, Winfried and Ruokonen, Aimo and Robertson, Neil R and Rzehak, Peter and Salomaa, Veikko and Sanders, Alan R and Sandhu, Manjinder S and Sanna, Serena and Saramies, Jouko and Savolainen, Markku J and Scherag, Susann and Schipf, Sabine and Schreiber, Stefan and Schunkert, Heribert and Silander, Kaisa and Sinisalo, Juha and Siscovick, David S and Smit, Jan H and Soranzo, Nicole and Sovio, Ulla and Stephens, Jonathan and Surakka, Ida and Swift, Amy J and Tammesoo, Mari-Liis and Tardif, Jean-Claude and Teder-Laving, Maris and Teslovich, Tanya M and Thompson, John R and Thomson, Brian and T{\"o}njes, Anke and Tuomi, Tiinamaija and van Meurs, Joyce B J and van Ommen, Gert-Jan and Vatin, Vincent and Viikari, Jorma and Visvikis-Siest, Sophie and Vitart, Veronique and Vogel, Carla I G and Voight, Benjamin F and Waite, Lindsay L and Wallaschofski, Henri and Walters, G Bragi and Widen, Elisabeth and Wiegand, Susanna and Wild, Sarah H and Willemsen, Gonneke and Witte, Daniel R and Witteman, Jacqueline C and Xu, Jianfeng and Zhang, Qunyuan and Zgaga, Lina and Ziegler, Andreas and Zitting, Paavo and Beilby, John P and Farooqi, I Sadaf and Hebebrand, Johannes and Huikuri, Heikki V and James, Alan L and K{\"a}h{\"o}nen, Mika and Levinson, Douglas F and Macciardi, Fabio and Nieminen, Markku S and Ohlsson, Claes and Palmer, Lyle J and Ridker, Paul M and Stumvoll, Michael and Beckmann, Jacques S and Boeing, Heiner and Boerwinkle, Eric and Boomsma, Dorret I and Caulfield, Mark J and Chanock, Stephen J and Collins, Francis S and Cupples, L Adrienne and Smith, George Davey and Erdmann, Jeanette and Froguel, Philippe and Gr{\"o}nberg, Henrik and Gyllensten, Ulf and Hall, Per and Hansen, Torben and Harris, Tamara B and Hattersley, Andrew T and Hayes, Richard B and Heinrich, Joachim and Hu, Frank B and Hveem, Kristian and Illig, Thomas and Jarvelin, Marjo-Riitta and Kaprio, Jaakko and Karpe, Fredrik and Khaw, Kay-Tee and Kiemeney, Lambertus A and Krude, Heiko and Laakso, Markku and Lawlor, Debbie A and Metspalu, Andres and Munroe, Patricia B and Ouwehand, Willem H and Pedersen, Oluf and Penninx, Brenda W and Peters, Annette and Pramstaller, Peter P and Quertermous, Thomas and Reinehr, Thomas and Rissanen, Aila and Rudan, Igor and Samani, Nilesh J and Schwarz, Peter E H and Shuldiner, Alan R and Spector, Timothy D and Tuomilehto, Jaakko and Uda, Manuela and Uitterlinden, Andre and Valle, Timo T and Wabitsch, Martin and Waeber, G{\'e}rard and Wareham, Nicholas J and Watkins, Hugh and Wilson, James F and Wright, Alan F and Zillikens, M Carola and Chatterjee, Nilanjan and McCarroll, Steven A and Purcell, Shaun and Schadt, Eric E and Visscher, Peter M and Assimes, Themistocles L and Borecki, Ingrid B and Deloukas, Panos and Fox, Caroline S and Groop, Leif C and Haritunians, Talin and Hunter, David J and Kaplan, Robert C and Mohlke, Karen L and O{\textquoteright}Connell, Jeffrey R and Peltonen, Leena and Schlessinger, David and Strachan, David P and van Duijn, Cornelia M and Wichmann, H-Erich and Frayling, Timothy M and Thorsteinsdottir, Unnur and Abecasis, Goncalo R and Barroso, In{\^e}s and Boehnke, Michael and Stefansson, Kari and North, Kari E and McCarthy, Mark I and Hirschhorn, Joel N and Ingelsson, Erik and Loos, Ruth J F} } @article {1221, title = {Biological, clinical and population relevance of 95 loci for blood lipids.}, journal = {Nature}, volume = {466}, year = {2010}, month = {2010 Aug 05}, pages = {707-13}, abstract = {

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

}, keywords = {African Americans, Animals, Asian Continental Ancestry Group, Cholesterol, HDL, Cholesterol, LDL, Coronary Artery Disease, Europe, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Lipid Metabolism, Lipids, Liver, Male, Mice, N-Acetylgalactosaminyltransferases, Phenotype, Polymorphism, Single Nucleotide, Protein Phosphatase 1, Reproducibility of Results, Triglycerides}, issn = {1476-4687}, doi = {10.1038/nature09270}, author = {Teslovich, Tanya M and Musunuru, Kiran and Smith, Albert V and Edmondson, Andrew C and Stylianou, Ioannis M and Koseki, Masahiro and Pirruccello, James P and Ripatti, Samuli and Chasman, Daniel I and Willer, Cristen J and Johansen, Christopher T and Fouchier, Sigrid W and Isaacs, Aaron and Peloso, Gina M and Barbalic, Maja and Ricketts, Sally L and Bis, Joshua C and Aulchenko, Yurii S and Thorleifsson, Gudmar and Feitosa, Mary F and Chambers, John and Orho-Melander, Marju and Melander, Olle and Johnson, Toby and Li, Xiaohui and Guo, Xiuqing and Li, Mingyao and Shin Cho, Yoon and Jin Go, Min and Jin Kim, Young and Lee, Jong-Young and Park, Taesung and Kim, Kyunga and Sim, Xueling and Twee-Hee Ong, Rick and Croteau-Chonka, Damien C and Lange, Leslie A and Smith, Joshua D and Song, Kijoung and Hua Zhao, Jing and Yuan, Xin and Luan, Jian{\textquoteright}an and Lamina, Claudia and Ziegler, Andreas and Zhang, Weihua and Zee, Robert Y L and Wright, Alan F and Witteman, Jacqueline C M and Wilson, James F and Willemsen, Gonneke and Wichmann, H-Erich and Whitfield, John B and Waterworth, Dawn M and Wareham, Nicholas J and Waeber, G{\'e}rard and Vollenweider, Peter and Voight, Benjamin F and Vitart, Veronique and Uitterlinden, Andr{\'e} G and Uda, Manuela and Tuomilehto, Jaakko and Thompson, John R and Tanaka, Toshiko and Surakka, Ida and Stringham, Heather M and Spector, Tim D and Soranzo, Nicole and Smit, Johannes H and Sinisalo, Juha and Silander, Kaisa and Sijbrands, Eric J G and Scuteri, Angelo and Scott, James and Schlessinger, David and Sanna, Serena and Salomaa, Veikko and Saharinen, Juha and Sabatti, Chiara and Ruokonen, Aimo and Rudan, Igor and Rose, Lynda M and Roberts, Robert and Rieder, Mark and Psaty, Bruce M and Pramstaller, Peter P and Pichler, Irene and Perola, Markus and Penninx, Brenda W J H and Pedersen, Nancy L and Pattaro, Cristian and Parker, Alex N and Par{\'e}, Guillaume and Oostra, Ben A and O{\textquoteright}Donnell, Christopher J and Nieminen, Markku S and Nickerson, Deborah A and Montgomery, Grant W and Meitinger, Thomas and McPherson, Ruth and McCarthy, Mark I and McArdle, Wendy and Masson, David and Martin, Nicholas G and Marroni, Fabio and Mangino, Massimo and Magnusson, Patrik K E and Lucas, Gavin and Luben, Robert and Loos, Ruth J F and Lokki, Marja-Liisa and Lettre, Guillaume and Langenberg, Claudia and Launer, Lenore J and Lakatta, Edward G and Laaksonen, Reijo and Kyvik, Kirsten O and Kronenberg, Florian and K{\"o}nig, Inke R and Khaw, Kay-Tee and Kaprio, Jaakko and Kaplan, Lee M and Johansson, Asa and Jarvelin, Marjo-Riitta and Janssens, A Cecile J W and Ingelsson, Erik and Igl, Wilmar and Kees Hovingh, G and Hottenga, Jouke-Jan and Hofman, Albert and Hicks, Andrew A and Hengstenberg, Christian and Heid, Iris M and Hayward, Caroline and Havulinna, Aki S and Hastie, Nicholas D and Harris, Tamara B and Haritunians, Talin and Hall, Alistair S and Gyllensten, Ulf and Guiducci, Candace and Groop, Leif C and Gonzalez, Elena and Gieger, Christian and Freimer, Nelson B and Ferrucci, Luigi and Erdmann, Jeanette and Elliott, Paul and Ejebe, Kenechi G and D{\"o}ring, Angela and Dominiczak, Anna F and Demissie, Serkalem and Deloukas, Panagiotis and de Geus, Eco J C and de Faire, Ulf and Crawford, Gabriel and Collins, Francis S and Chen, Yii-der I and Caulfield, Mark J and Campbell, Harry and Burtt, Noel P and Bonnycastle, Lori L and Boomsma, Dorret I and Boekholdt, S Matthijs and Bergman, Richard N and Barroso, In{\^e}s and Bandinelli, Stefania and Ballantyne, Christie M and Assimes, Themistocles L and Quertermous, Thomas and Altshuler, David and Seielstad, Mark and Wong, Tien Y and Tai, E-Shyong and Feranil, Alan B and Kuzawa, Christopher W and Adair, Linda S and Taylor, Herman A and Borecki, Ingrid B and Gabriel, Stacey B and Wilson, James G and Holm, Hilma and Thorsteinsdottir, Unnur and Gudnason, Vilmundur and Krauss, Ronald M and Mohlke, Karen L and Ordovas, Jose M and Munroe, Patricia B and Kooner, Jaspal S and Tall, Alan R and Hegele, Robert A and Kastelein, John J P and Schadt, Eric E and Rotter, Jerome I and Boerwinkle, Eric and Strachan, David P and Mooser, Vincent and Stefansson, Kari and Reilly, Muredach P and Samani, Nilesh J and Schunkert, Heribert and Cupples, L Adrienne and Sandhu, Manjinder S and Ridker, Paul M and Rader, Daniel J and van Duijn, Cornelia M and Peltonen, Leena and Abecasis, Goncalo R and Boehnke, Michael and Kathiresan, Sekar} } @article {1243, title = {Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.}, journal = {PLoS Genet}, volume = {6}, year = {2010}, month = {2010 Oct 28}, pages = {e1001184}, abstract = {

There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n  =  6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0{\texttimes}10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0\%-3.2\% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p  =  1.61{\texttimes}10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25{\texttimes}10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p  =  2.15{\texttimes}10(-13), in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32{\texttimes}10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Child, Child, Preschool, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 19, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Cohort Studies, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Microcirculation, Middle Aged, Polymorphism, Single Nucleotide, Retinal Vessels, Young Adult}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1001184}, author = {Ikram, M Kamran and Sim, Xueling and Xueling, Sim and Jensen, Richard A and Cotch, Mary Frances and Hewitt, Alex W and Ikram, M Arfan and Wang, Jie Jin and Klein, Ronald and Klein, Barbara E K and Breteler, Monique M B and Cheung, Ning and Liew, Gerald and Mitchell, Paul and Uitterlinden, Andr{\'e} G and Rivadeneira, Fernando and Hofman, Albert and de Jong, Paulus T V M and van Duijn, Cornelia M and Kao, Linda and Cheng, Ching-Yu and Smith, Albert Vernon and Glazer, Nicole L and Lumley, Thomas and McKnight, Barbara and Psaty, Bruce M and Jonasson, Fridbert and Eiriksdottir, Gudny and Aspelund, Thor and Harris, Tamara B and Launer, Lenore J and Taylor, Kent D and Li, Xiaohui and Iyengar, Sudha K and Xi, Quansheng and Sivakumaran, Theru A and Mackey, David A and Macgregor, Stuart and Martin, Nicholas G and Young, Terri L and Bis, Josh C and Wiggins, Kerri L and Heckbert, Susan R and Hammond, Christopher J and Andrew, Toby and Fahy, Samantha and Attia, John and Holliday, Elizabeth G and Scott, Rodney J and Islam, F M Amirul and Rotter, Jerome I and McAuley, Annie K and Boerwinkle, Eric and Tai, E Shyong and Gudnason, Vilmundur and Siscovick, David S and Vingerling, Johannes R and Wong, Tien Y} } @article {1234, title = {Hundreds of variants clustered in genomic loci and biological pathways affect human height.}, journal = {Nature}, volume = {467}, year = {2010}, month = {2010 Oct 14}, pages = {832-8}, abstract = {

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10\% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16\% of phenotypic variation (approximately 20\% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

}, keywords = {Body Height, Chromosomes, Human, Pair 3, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Metabolic Networks and Pathways, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide}, issn = {1476-4687}, doi = {10.1038/nature09410}, author = {Lango Allen, Hana and Estrada, Karol and Lettre, Guillaume and Berndt, Sonja I and Weedon, Michael N and Rivadeneira, Fernando and Willer, Cristen J and Jackson, Anne U and Vedantam, Sailaja and Raychaudhuri, Soumya and Ferreira, Teresa and Wood, Andrew R and Weyant, Robert J and Segr{\`e}, Ayellet V and Speliotes, Elizabeth K and Wheeler, Eleanor and Soranzo, Nicole and Park, Ju-Hyun and Yang, Jian and Gudbjartsson, Daniel and Heard-Costa, Nancy L and Randall, Joshua C and Qi, Lu and Vernon Smith, Albert and M{\"a}gi, Reedik and Pastinen, Tomi and Liang, Liming and Heid, Iris M and Luan, Jian{\textquoteright}an and Thorleifsson, Gudmar and Winkler, Thomas W and Goddard, Michael E and Sin Lo, Ken and Palmer, Cameron and Workalemahu, Tsegaselassie and Aulchenko, Yurii S and Johansson, Asa and Zillikens, M Carola and Feitosa, Mary F and Esko, T{\~o}nu and Johnson, Toby and Ketkar, Shamika and Kraft, Peter and Mangino, Massimo and Prokopenko, Inga and Absher, Devin and Albrecht, Eva and Ernst, Florian and Glazer, Nicole L and Hayward, Caroline and Hottenga, Jouke-Jan and Jacobs, Kevin B and Knowles, Joshua W and Kutalik, Zolt{\'a}n and Monda, Keri L and Polasek, Ozren and Preuss, Michael and Rayner, Nigel W and Robertson, Neil R and Steinthorsdottir, Valgerdur and Tyrer, Jonathan P and Voight, Benjamin F and Wiklund, Fredrik and Xu, Jianfeng and Zhao, Jing Hua and Nyholt, Dale R and Pellikka, Niina and Perola, Markus and Perry, John R B and Surakka, Ida and Tammesoo, Mari-Liis and Altmaier, Elizabeth L and Amin, Najaf and Aspelund, Thor and Bhangale, Tushar and Boucher, Gabrielle and Chasman, Daniel I and Chen, Constance and Coin, Lachlan and Cooper, Matthew N and Dixon, Anna L and Gibson, Quince and Grundberg, Elin and Hao, Ke and Juhani Junttila, M and Kaplan, Lee M and Kettunen, Johannes and K{\"o}nig, Inke R and Kwan, Tony and Lawrence, Robert W and Levinson, Douglas F and Lorentzon, Mattias and McKnight, Barbara and Morris, Andrew P and M{\"u}ller, Martina and Suh Ngwa, Julius and Purcell, Shaun and Rafelt, Suzanne and Salem, Rany M and Salvi, Erika and Sanna, Serena and Shi, Jianxin and Sovio, Ulla and Thompson, John R and Turchin, Michael C and Vandenput, Liesbeth and Verlaan, Dominique J and Vitart, Veronique and White, Charles C and Ziegler, Andreas and Almgren, Peter and Balmforth, Anthony J and Campbell, Harry and Citterio, Lorena and De Grandi, Alessandro and Dominiczak, Anna and Duan, Jubao and Elliott, Paul and Elosua, Roberto and Eriksson, Johan G and Freimer, Nelson B and Geus, Eco J C and Glorioso, Nicola and Haiqing, Shen and Hartikainen, Anna-Liisa and Havulinna, Aki S and Hicks, Andrew A and Hui, Jennie and Igl, Wilmar and Illig, Thomas and Jula, Antti and Kajantie, Eero and Kilpel{\"a}inen, Tuomas O and Koiranen, Markku and Kolcic, Ivana and Koskinen, Seppo and Kovacs, Peter and Laitinen, Jaana and Liu, Jianjun and Lokki, Marja-Liisa and Marusic, Ana and Maschio, Andrea and Meitinger, Thomas and Mulas, Antonella and Par{\'e}, Guillaume and Parker, Alex N and Peden, John F and Petersmann, Astrid and Pichler, Irene and Pietil{\"a}inen, Kirsi H and Pouta, Anneli and Ridderstr{\r a}le, Martin and Rotter, Jerome I and Sambrook, Jennifer G and Sanders, Alan R and Schmidt, Carsten Oliver and Sinisalo, Juha and Smit, Jan H and Stringham, Heather M and Bragi Walters, G and Widen, Elisabeth and Wild, Sarah H and Willemsen, Gonneke and Zagato, Laura and Zgaga, Lina and Zitting, Paavo and Alavere, Helene and Farrall, Martin and McArdle, Wendy L and Nelis, Mari and Peters, Marjolein J and Ripatti, Samuli and van Meurs, Joyce B J and Aben, Katja K and Ardlie, Kristin G and Beckmann, Jacques S and Beilby, John P and Bergman, Richard N and Bergmann, Sven and Collins, Francis S and Cusi, Daniele and den Heijer, Martin and Eiriksdottir, Gudny and Gejman, Pablo V and Hall, Alistair S and Hamsten, Anders and Huikuri, Heikki V and Iribarren, Carlos and K{\"a}h{\"o}nen, Mika and Kaprio, Jaakko and Kathiresan, Sekar and Kiemeney, Lambertus and Kocher, Thomas and Launer, Lenore J and Lehtim{\"a}ki, Terho and Melander, Olle and Mosley, Tom H and Musk, Arthur W and Nieminen, Markku S and O{\textquoteright}Donnell, Christopher J and Ohlsson, Claes and Oostra, Ben and Palmer, Lyle J and Raitakari, Olli and Ridker, Paul M and Rioux, John D and Rissanen, Aila and Rivolta, Carlo and Schunkert, Heribert and Shuldiner, Alan R and Siscovick, David S and Stumvoll, Michael and T{\"o}njes, Anke and Tuomilehto, Jaakko and van Ommen, Gert-Jan and Viikari, Jorma and Heath, Andrew C and Martin, Nicholas G and Montgomery, Grant W and Province, Michael A and Kayser, Manfred and Arnold, Alice M and Atwood, Larry D and Boerwinkle, Eric and Chanock, Stephen J and Deloukas, Panos and Gieger, Christian and Gr{\"o}nberg, Henrik and Hall, Per and Hattersley, Andrew T and Hengstenberg, Christian and Hoffman, Wolfgang and Lathrop, G Mark and Salomaa, Veikko and Schreiber, Stefan and Uda, Manuela and Waterworth, Dawn and Wright, Alan F and Assimes, Themistocles L and Barroso, In{\^e}s and Hofman, Albert and Mohlke, Karen L and Boomsma, Dorret I and Caulfield, Mark J and Cupples, L Adrienne and Erdmann, Jeanette and Fox, Caroline S and Gudnason, Vilmundur and Gyllensten, Ulf and Harris, Tamara B and Hayes, Richard B and Jarvelin, Marjo-Riitta and Mooser, Vincent and Munroe, Patricia B and Ouwehand, Willem H and Penninx, Brenda W and Pramstaller, Peter P and Quertermous, Thomas and Rudan, Igor and Samani, Nilesh J and Spector, Timothy D and V{\"o}lzke, Henry and Watkins, Hugh and Wilson, James F and Groop, Leif C and Haritunians, Talin and Hu, Frank B and Kaplan, Robert C and Metspalu, Andres and North, Kari E and Schlessinger, David and Wareham, Nicholas J and Hunter, David J and O{\textquoteright}Connell, Jeffrey R and Strachan, David P and Wichmann, H-Erich and Borecki, Ingrid B and van Duijn, Cornelia M and Schadt, Eric E and Thorsteinsdottir, Unnur and Peltonen, Leena and Uitterlinden, Andr{\'e} G and Visscher, Peter M and Chatterjee, Nilanjan and Loos, Ruth J F and Boehnke, Michael and McCarthy, Mark I and Ingelsson, Erik and Lindgren, Cecilia M and Abecasis, Goncalo R and Stefansson, Kari and Frayling, Timothy M and Hirschhorn, Joel N} } @article {1355, title = {New gene functions in megakaryopoiesis and platelet formation.}, journal = {Nature}, volume = {480}, year = {2011}, month = {2011 Nov 30}, pages = {201-8}, abstract = {

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.

}, keywords = {Animals, Blood Platelets, Cell Size, Drosophila melanogaster, Drosophila Proteins, Europe, Gene Expression Profiling, Gene Silencing, Genome, Human, Genome-Wide Association Study, Hematopoiesis, Humans, Megakaryocytes, Platelet Count, Protein Interaction Maps, Transcription, Genetic, Zebrafish, Zebrafish Proteins}, issn = {1476-4687}, doi = {10.1038/nature10659}, author = {Gieger, Christian and Radhakrishnan, Aparna and Cvejic, Ana and Tang, Weihong and Porcu, Eleonora and Pistis, Giorgio and Serbanovic-Canic, Jovana and Elling, Ulrich and Goodall, Alison H and Labrune, Yann and Lopez, Lorna M and M{\"a}gi, Reedik and Meacham, Stuart and Okada, Yukinori and Pirastu, Nicola and Sorice, Rossella and Teumer, Alexander and Voss, Katrin and Zhang, Weihua and Ramirez-Solis, Ramiro and Bis, Joshua C and Ellinghaus, David and G{\"o}gele, Martin and Hottenga, Jouke-Jan and Langenberg, Claudia and Kovacs, Peter and O{\textquoteright}Reilly, Paul F and Shin, So-Youn and Esko, T{\~o}nu and Hartiala, Jaana and Kanoni, Stavroula and Murgia, Federico and Parsa, Afshin and Stephens, Jonathan and van der Harst, Pim and Ellen van der Schoot, C and Allayee, Hooman and Attwood, Antony and Balkau, Beverley and Bastardot, Fran{\c c}ois and Basu, Saonli and Baumeister, Sebastian E and Biino, Ginevra and Bomba, Lorenzo and Bonnefond, Am{\'e}lie and Cambien, Francois and Chambers, John C and Cucca, Francesco and D{\textquoteright}Adamo, Pio and Davies, Gail and de Boer, Rudolf A and de Geus, Eco J C and D{\"o}ring, Angela and Elliott, Paul and Erdmann, Jeanette and Evans, David M and Falchi, Mario and Feng, Wei and Folsom, Aaron R and Frazer, Ian H and Gibson, Quince D and Glazer, Nicole L and Hammond, Chris and Hartikainen, Anna-Liisa and Heckbert, Susan R and Hengstenberg, Christian and Hersch, Micha and Illig, Thomas and Loos, Ruth J F and Jolley, Jennifer and Khaw, Kay Tee and Kuhnel, Brigitte and Kyrtsonis, Marie-Christine and Lagou, Vasiliki and Lloyd-Jones, Heather and Lumley, Thomas and Mangino, Massimo and Maschio, Andrea and Mateo Leach, Irene and McKnight, Barbara and Memari, Yasin and Mitchell, Braxton D and Montgomery, Grant W and Nakamura, Yusuke and Nauck, Matthias and Navis, Gerjan and N{\"o}thlings, Ute and Nolte, Ilja M and Porteous, David J and Pouta, Anneli and Pramstaller, Peter P and Pullat, Janne and Ring, Susan M and Rotter, Jerome I and Ruggiero, Daniela and Ruokonen, Aimo and Sala, Cinzia and Samani, Nilesh J and Sambrook, Jennifer and Schlessinger, David and Schreiber, Stefan and Schunkert, Heribert and Scott, James and Smith, Nicholas L and Snieder, Harold and Starr, John M and Stumvoll, Michael and Takahashi, Atsushi and Tang, W H Wilson and Taylor, Kent and Tenesa, Albert and Lay Thein, Swee and T{\"o}njes, Anke and Uda, Manuela and Ulivi, Sheila and van Veldhuisen, Dirk J and Visscher, Peter M and V{\"o}lker, Uwe and Wichmann, H-Erich and Wiggins, Kerri L and Willemsen, Gonneke and Yang, Tsun-Po and Hua Zhao, Jing and Zitting, Paavo and Bradley, John R and Dedoussis, George V and Gasparini, Paolo and Hazen, Stanley L and Metspalu, Andres and Pirastu, Mario and Shuldiner, Alan R and Joost van Pelt, L and Zwaginga, Jaap-Jan and Boomsma, Dorret I and Deary, Ian J and Franke, Andre and Froguel, Philippe and Ganesh, Santhi K and Jarvelin, Marjo-Riitta and Martin, Nicholas G and Meisinger, Christa and Psaty, Bruce M and Spector, Timothy D and Wareham, Nicholas J and Akkerman, Jan-Willem N and Ciullo, Marina and Deloukas, Panos and Greinacher, Andreas and Jupe, Steve and Kamatani, Naoyuki and Khadake, Jyoti and Kooner, Jaspal S and Penninger, Josef and Prokopenko, Inga and Stemple, Derek and Toniolo, Daniela and Wernisch, Lorenz and Sanna, Serena and Hicks, Andrew A and Rendon, Augusto and Ferreira, Manuel A and Ouwehand, Willem H and Soranzo, Nicole} } @article {6175, title = {FTO genotype is associated with phenotypic variability of body mass index.}, journal = {Nature}, volume = {490}, year = {2012}, month = {2012 Oct 11}, pages = {267-72}, abstract = {

There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using \~{}170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7\%, corresponding to a difference of \~{}0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI, possibly mediated by DNA methylation. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

}, keywords = {Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Body Height, Body Mass Index, Co-Repressor Proteins, Female, Genetic Variation, Genome-Wide Association Study, Humans, Male, Nerve Tissue Proteins, Phenotype, Polymorphism, Single Nucleotide, Proteins, Repressor Proteins}, issn = {1476-4687}, doi = {10.1038/nature11401}, author = {Yang, Jian and Loos, Ruth J F and Powell, Joseph E and Medland, Sarah E and Speliotes, Elizabeth K and Chasman, Daniel I and Rose, Lynda M and Thorleifsson, Gudmar and Steinthorsdottir, Valgerdur and M{\"a}gi, Reedik and Waite, Lindsay and Smith, Albert Vernon and Yerges-Armstrong, Laura M and Monda, Keri L and Hadley, David and Mahajan, Anubha and Li, Guo and Kapur, Karen and Vitart, Veronique and Huffman, Jennifer E and Wang, Sophie R and Palmer, Cameron and Esko, T{\~o}nu and Fischer, Krista and Zhao, Jing Hua and Demirkan, Ayse and Isaacs, Aaron and Feitosa, Mary F and Luan, Jian{\textquoteright}an and Heard-Costa, Nancy L and White, Charles and Jackson, Anne U and Preuss, Michael and Ziegler, Andreas and Eriksson, Joel and Kutalik, Zolt{\'a}n and Frau, Francesca and Nolte, Ilja M and van Vliet-Ostaptchouk, Jana V and Hottenga, Jouke-Jan and Jacobs, Kevin B and Verweij, Niek and Goel, Anuj and Medina-G{\'o}mez, Carolina and Estrada, Karol and Bragg-Gresham, Jennifer Lynn and Sanna, Serena and Sidore, Carlo and Tyrer, Jonathan and Teumer, Alexander and Prokopenko, Inga and Mangino, Massimo and Lindgren, Cecilia M and Assimes, Themistocles L and Shuldiner, Alan R and Hui, Jennie and Beilby, John P and McArdle, Wendy L and Hall, Per and Haritunians, Talin and Zgaga, Lina and Kolcic, Ivana and Polasek, Ozren and Zemunik, Tatijana and Oostra, Ben A and Junttila, M Juhani and Gr{\"o}nberg, Henrik and Schreiber, Stefan and Peters, Annette and Hicks, Andrew A and Stephens, Jonathan and Foad, Nicola S and Laitinen, Jaana and Pouta, Anneli and Kaakinen, Marika and Willemsen, Gonneke and Vink, Jacqueline M and Wild, Sarah H and Navis, Gerjan and Asselbergs, Folkert W and Homuth, Georg and John, Ulrich and Iribarren, Carlos and Harris, Tamara and Launer, Lenore and Gudnason, Vilmundur and O{\textquoteright}Connell, Jeffrey R and Boerwinkle, Eric and Cadby, Gemma and Palmer, Lyle J and James, Alan L and Musk, Arthur W and Ingelsson, Erik and Psaty, Bruce M and Beckmann, Jacques S and Waeber, G{\'e}rard and Vollenweider, Peter and Hayward, Caroline and Wright, Alan F and Rudan, Igor and Groop, Leif C and Metspalu, Andres and Khaw, Kay Tee and van Duijn, Cornelia M and Borecki, Ingrid B and Province, Michael A and Wareham, Nicholas J and Tardif, Jean-Claude and Huikuri, Heikki V and Cupples, L Adrienne and Atwood, Larry D and Fox, Caroline S and Boehnke, Michael and Collins, Francis S and Mohlke, Karen L and Erdmann, Jeanette and Schunkert, Heribert and Hengstenberg, Christian and Stark, Klaus and Lorentzon, Mattias and Ohlsson, Claes and Cusi, Daniele and Staessen, Jan A and van der Klauw, Melanie M and Pramstaller, Peter P and Kathiresan, Sekar and Jolley, Jennifer D and Ripatti, Samuli and Jarvelin, Marjo-Riitta and de Geus, Eco J C and Boomsma, Dorret I and Penninx, Brenda and Wilson, James F and Campbell, Harry and Chanock, Stephen J and van der Harst, Pim and Hamsten, Anders and Watkins, Hugh and Hofman, Albert and Witteman, Jacqueline C and Zillikens, M Carola and Uitterlinden, Andr{\'e} G and Rivadeneira, Fernando and Zillikens, M Carola and Kiemeney, Lambertus A and Vermeulen, Sita H and Abecasis, Goncalo R and Schlessinger, David and Schipf, Sabine and Stumvoll, Michael and T{\"o}njes, Anke and Spector, Tim D and North, Kari E and Lettre, Guillaume and McCarthy, Mark I and Berndt, Sonja I and Heath, Andrew C and Madden, Pamela A F and Nyholt, Dale R and Montgomery, Grant W and Martin, Nicholas G and McKnight, Barbara and Strachan, David P and Hill, William G and Snieder, Harold and Ridker, Paul M and Thorsteinsdottir, Unnur and Stefansson, Kari and Frayling, Timothy M and Hirschhorn, Joel N and Goddard, Michael E and Visscher, Peter M} } @article {1360, title = {Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.}, journal = {Nat Genet}, volume = {44}, year = {2012}, month = {2012 Jan 22}, pages = {260-8}, abstract = {

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 {\texttimes} 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

}, keywords = {Age Factors, DNA Helicases, DNA Polymerase gamma, DNA Primase, DNA Repair, DNA Repair Enzymes, DNA-Directed DNA Polymerase, European Continental Ancestry Group, Exodeoxyribonucleases, Female, Genetic Loci, Genome-Wide Association Study, Humans, Immunity, Menopause, Polymorphism, Single Nucleotide, Proteins}, issn = {1546-1718}, doi = {10.1038/ng.1051}, author = {Stolk, Lisette and Perry, John R B and Chasman, Daniel I and He, Chunyan and Mangino, Massimo and Sulem, Patrick and Barbalic, Maja and Broer, Linda and Byrne, Enda M and Ernst, Florian and Esko, T{\~o}nu and Franceschini, Nora and Gudbjartsson, Daniel F and Hottenga, Jouke-Jan and Kraft, Peter and McArdle, Patrick F and Porcu, Eleonora and Shin, So-Youn and Smith, Albert V and van Wingerden, Sophie and Zhai, Guangju and Zhuang, Wei V and Albrecht, Eva and Alizadeh, Behrooz Z and Aspelund, Thor and Bandinelli, Stefania and Lauc, Lovorka Barac and Beckmann, Jacques S and Boban, Mladen and Boerwinkle, Eric and Broekmans, Frank J and Burri, Andrea and Campbell, Harry and Chanock, Stephen J and Chen, Constance and Cornelis, Marilyn C and Corre, Tanguy and Coviello, Andrea D and D{\textquoteright}Adamo, Pio and Davies, Gail and de Faire, Ulf and de Geus, Eco J C and Deary, Ian J and Dedoussis, George V Z and Deloukas, Panagiotis and Ebrahim, Shah and Eiriksdottir, Gudny and Emilsson, Valur and Eriksson, Johan G and Fauser, Bart C J M and Ferreli, Liana and Ferrucci, Luigi and Fischer, Krista and Folsom, Aaron R and Garcia, Melissa E and Gasparini, Paolo and Gieger, Christian and Glazer, Nicole and Grobbee, Diederick E and Hall, Per and Haller, Toomas and Hankinson, Susan E and Hass, Merli and Hayward, Caroline and Heath, Andrew C and Hofman, Albert and Ingelsson, Erik and Janssens, A Cecile J W and Johnson, Andrew D and Karasik, David and Kardia, Sharon L R and Keyzer, Jules and Kiel, Douglas P and Kolcic, Ivana and Kutalik, Zolt{\'a}n and Lahti, Jari and Lai, Sandra and Laisk, Triin and Laven, Joop S E and Lawlor, Debbie A and Liu, Jianjun and Lopez, Lorna M and Louwers, Yvonne V and Magnusson, Patrik K E and Marongiu, Mara and Martin, Nicholas G and Klaric, Irena Martinovic and Masciullo, Corrado and McKnight, Barbara and Medland, Sarah E and Melzer, David and Mooser, Vincent and Navarro, Pau and Newman, Anne B and Nyholt, Dale R and Onland-Moret, N Charlotte and Palotie, Aarno and Par{\'e}, Guillaume and Parker, Alex N and Pedersen, Nancy L and Peeters, Petra H M and Pistis, Giorgio and Plump, Andrew S and Polasek, Ozren and Pop, Victor J M and Psaty, Bruce M and R{\"a}ikk{\"o}nen, Katri and Rehnberg, Emil and Rotter, Jerome I and Rudan, Igor and Sala, Cinzia and Salumets, Andres and Scuteri, Angelo and Singleton, Andrew and Smith, Jennifer A and Snieder, Harold and Soranzo, Nicole and Stacey, Simon N and Starr, John M and Stathopoulou, Maria G and Stirrups, Kathleen and Stolk, Ronald P and Styrkarsdottir, Unnur and Sun, Yan V and Tenesa, Albert and Thorand, Barbara and Toniolo, Daniela and Tryggvadottir, Laufey and Tsui, Kim and Ulivi, Sheila and van Dam, Rob M and van der Schouw, Yvonne T and van Gils, Carla H and van Nierop, Peter and Vink, Jacqueline M and Visscher, Peter M and Voorhuis, Marlies and Waeber, G{\'e}rard and Wallaschofski, Henri and Wichmann, H Erich and Widen, Elisabeth and Wijnands-van Gent, Colette J M and Willemsen, Gonneke and Wilson, James F and Wolffenbuttel, Bruce H R and Wright, Alan F and Yerges-Armstrong, Laura M and Zemunik, Tatijana and Zgaga, Lina and Zillikens, M Carola and Zygmunt, Marek and Arnold, Alice M and Boomsma, Dorret I and Buring, Julie E and Crisponi, Laura and Demerath, Ellen W and Gudnason, Vilmundur and Harris, Tamara B and Hu, Frank B and Hunter, David J and Launer, Lenore J and Metspalu, Andres and Montgomery, Grant W and Oostra, Ben A and Ridker, Paul M and Sanna, Serena and Schlessinger, David and Spector, Tim D and Stefansson, Kari and Streeten, Elizabeth A and Thorsteinsdottir, Unnur and Uda, Manuela and Uitterlinden, Andr{\'e} G and van Duijn, Cornelia M and V{\"o}lzke, Henry and Murray, Anna and Murabito, Joanne M and Visser, Jenny A and Lunetta, Kathryn L} } @article {1378, title = {Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.}, journal = {PLoS Genet}, volume = {8}, year = {2012}, month = {2012}, pages = {e1002607}, abstract = {

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5{\texttimes}10(-8)-1.2{\texttimes}10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3{\texttimes}10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3{\texttimes}10(-3), n = 22,044), increased triglycerides (p = 2.6{\texttimes}10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8{\texttimes}10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4{\texttimes}10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5{\texttimes}10(-13), n = 96,748) and decreased BMI (p = 1.4{\texttimes}10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

}, keywords = {Adiponectin, African Americans, Asian Continental Ancestry Group, Cholesterol, HDL, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Insulin Resistance, Male, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1002607}, author = {Dastani, Zari and Hivert, Marie-France and Timpson, Nicholas and Perry, John R B and Yuan, Xin and Scott, Robert A and Henneman, Peter and Heid, Iris M and Kizer, Jorge R and Lyytik{\"a}inen, Leo-Pekka and Fuchsberger, Christian and Tanaka, Toshiko and Morris, Andrew P and Small, Kerrin and Isaacs, Aaron and Beekman, Marian and Coassin, Stefan and Lohman, Kurt and Qi, Lu and Kanoni, Stavroula and Pankow, James S and Uh, Hae-Won and Wu, Ying and Bidulescu, Aurelian and Rasmussen-Torvik, Laura J and Greenwood, Celia M T and Ladouceur, Martin and Grimsby, Jonna and Manning, Alisa K and Liu, Ching-Ti and Kooner, Jaspal and Mooser, Vincent E and Vollenweider, Peter and Kapur, Karen A and Chambers, John and Wareham, Nicholas J and Langenberg, Claudia and Frants, Rune and Willems-Vandijk, Ko and Oostra, Ben A and Willems, Sara M and Lamina, Claudia and Winkler, Thomas W and Psaty, Bruce M and Tracy, Russell P and Brody, Jennifer and Chen, Ida and Viikari, Jorma and K{\"a}h{\"o}nen, Mika and Pramstaller, Peter P and Evans, David M and St Pourcain, Beate and Sattar, Naveed and Wood, Andrew R and Bandinelli, Stefania and Carlson, Olga D and Egan, Josephine M and B{\"o}hringer, Stefan and van Heemst, Diana and Kedenko, Lyudmyla and Kristiansson, Kati and Nuotio, Marja-Liisa and Loo, Britt-Marie and Harris, Tamara and Garcia, Melissa and Kanaya, Alka and Haun, Margot and Klopp, Norman and Wichmann, H-Erich and Deloukas, Panos and Katsareli, Efi and Couper, David J and Duncan, Bruce B and Kloppenburg, Margreet and Adair, Linda S and Borja, Judith B and Wilson, James G and Musani, Solomon and Guo, Xiuqing and Johnson, Toby and Semple, Robert and Teslovich, Tanya M and Allison, Matthew A and Redline, Susan and Buxbaum, Sarah G and Mohlke, Karen L and Meulenbelt, Ingrid and Ballantyne, Christie M and Dedoussis, George V and Hu, Frank B and Liu, Yongmei and Paulweber, Bernhard and Spector, Timothy D and Slagboom, P Eline and Ferrucci, Luigi and Jula, Antti and Perola, Markus and Raitakari, Olli and Florez, Jose C and Salomaa, Veikko and Eriksson, Johan G and Frayling, Timothy M and Hicks, Andrew A and Lehtim{\"a}ki, Terho and Smith, George Davey and Siscovick, David S and Kronenberg, Florian and van Duijn, Cornelia and Loos, Ruth J F and Waterworth, Dawn M and Meigs, James B and Dupuis, Jos{\'e}e and Richards, J Brent and Voight, Benjamin F and Scott, Laura J and Steinthorsdottir, Valgerdur and Dina, Christian and Welch, Ryan P and Zeggini, Eleftheria and Huth, Cornelia and Aulchenko, Yurii S and Thorleifsson, Gudmar and McCulloch, Laura J and Ferreira, Teresa and Grallert, Harald and Amin, Najaf and Wu, Guanming and Willer, Cristen J and Raychaudhuri, Soumya and McCarroll, Steve A and Hofmann, Oliver M and Segr{\`e}, Ayellet V and van Hoek, Mandy and Navarro, Pau and Ardlie, Kristin and Balkau, Beverley and Benediktsson, Rafn and Bennett, Amanda J and Blagieva, Roza and Boerwinkle, Eric and Bonnycastle, Lori L and Bostr{\"o}m, Kristina Bengtsson and Bravenboer, Bert and Bumpstead, Suzannah and Burtt, Noel P and Charpentier, Guillaume and Chines, Peter S and Cornelis, Marilyn and Crawford, Gabe and Doney, Alex S F and Elliott, Katherine S and Elliott, Amanda L and Erdos, Michael R and Fox, Caroline S and Franklin, Christopher S and Ganser, Martha and Gieger, Christian and Grarup, Niels and Green, Todd and Griffin, Simon and Groves, Christopher J and Guiducci, Candace and Hadjadj, Samy and Hassanali, Neelam and Herder, Christian and Isomaa, Bo and Jackson, Anne U and Johnson, Paul R V and J{\o}rgensen, Torben and Kao, Wen H L and Kong, Augustine and Kraft, Peter and Kuusisto, Johanna and Lauritzen, Torsten and Li, Man and Lieverse, Aloysius and Lindgren, Cecilia M and Lyssenko, Valeriya and Marre, Michel and Meitinger, Thomas and Midthjell, Kristian and Morken, Mario A and Narisu, Narisu and Nilsson, Peter and Owen, Katharine R and Payne, Felicity and Petersen, Ann-Kristin and Platou, Carl and Proen{\c c}a, Christine and Prokopenko, Inga and Rathmann, Wolfgang and Rayner, N William and Robertson, Neil R and Rocheleau, Ghislain and Roden, Michael and Sampson, Michael J and Saxena, Richa and Shields, Beverley M and Shrader, Peter and Sigurdsson, Gunnar and Spars{\o}, Thomas and Strassburger, Klaus and Stringham, Heather M and Sun, Qi and Swift, Amy J and Thorand, Barbara and Tichet, Jean and Tuomi, Tiinamaija and van Dam, Rob M and van Haeften, Timon W and van Herpt, Thijs and van Vliet-Ostaptchouk, Jana V and Walters, G Bragi and Weedon, Michael N and Wijmenga, Cisca and Witteman, Jacqueline and Bergman, Richard N and Cauchi, Stephane and Collins, Francis S and Gloyn, Anna L and Gyllensten, Ulf and Hansen, Torben and Hide, Winston A and Hitman, Graham A and Hofman, Albert and Hunter, David J and Hveem, Kristian and Laakso, Markku and Morris, Andrew D and Palmer, Colin N A and Rudan, Igor and Sijbrands, Eric and Stein, Lincoln D and Tuomilehto, Jaakko and Uitterlinden, Andre and Walker, Mark and Watanabe, Richard M and Abecasis, Goncalo R and Boehm, Bernhard O and Campbell, Harry and Daly, Mark J and Hattersley, Andrew T and Pedersen, Oluf and Barroso, In{\^e}s and Groop, Leif and Sladek, Rob and Thorsteinsdottir, Unnur and Wilson, James F and Illig, Thomas and Froguel, Philippe and van Duijn, Cornelia M and Stefansson, Kari and Altshuler, David and Boehnke, Michael and McCarthy, Mark I and Soranzo, Nicole and Wheeler, Eleanor and Glazer, Nicole L and Bouatia-Naji, Nabila and M{\"a}gi, Reedik and Randall, Joshua and Elliott, Paul and Rybin, Denis and Dehghan, Abbas and Hottenga, Jouke Jan and Song, Kijoung and Goel, Anuj and Lajunen, Taina and Doney, Alex and Cavalcanti-Proen{\c c}a, Christine and Kumari, Meena and Timpson, Nicholas J and Zabena, Carina and Ingelsson, Erik and An, Ping and O{\textquoteright}Connell, Jeffrey and Luan, Jian{\textquoteright}an and Elliott, Amanda and McCarroll, Steven A and Roccasecca, Rosa Maria and Pattou, Fran{\c c}ois and Sethupathy, Praveen and Ariyurek, Yavuz and Barter, Philip and Beilby, John P and Ben-Shlomo, Yoav and Bergmann, Sven and Bochud, Murielle and Bonnefond, Am{\'e}lie and Borch-Johnsen, Knut and B{\"o}ttcher, Yvonne and Brunner, Eric and Bumpstead, Suzannah J and Chen, Yii-Der Ida and Chines, Peter and Clarke, Robert and Coin, Lachlan J M and Cooper, Matthew N and Crisponi, Laura and Day, Ian N M and de Geus, Eco J C and Delplanque, Jerome and Fedson, Annette C and Fischer-Rosinsky, Antje and Forouhi, Nita G and Franzosi, Maria Grazia and Galan, Pilar and Goodarzi, Mark O and Graessler, J{\"u}rgen and Grundy, Scott and Gwilliam, Rhian and Hallmans, G{\"o}ran and Hammond, Naomi and Han, Xijing and Hartikainen, Anna-Liisa and Hayward, Caroline and Heath, Simon C and Hercberg, Serge and Hillman, David R and Hingorani, Aroon D and Hui, Jennie and Hung, Joe and Kaakinen, Marika and Kaprio, Jaakko and Kesaniemi, Y Antero and Kivimaki, Mika and Knight, Beatrice and Koskinen, Seppo and Kovacs, Peter and Kyvik, Kirsten Ohm and Lathrop, G Mark and Lawlor, Debbie A and Le Bacquer, Olivier and Lecoeur, C{\'e}cile and Li, Yun and Mahley, Robert and Mangino, Massimo and Mart{\'\i}nez-Larrad, Mar{\'\i}a Teresa and McAteer, Jarred B and McPherson, Ruth and Meisinger, Christa and Melzer, David and Meyre, David and Mitchell, Braxton D and Mukherjee, Sutapa and Naitza, Silvia and Neville, Matthew J and Orr{\`u}, Marco and Pakyz, Ruth and Paolisso, Giuseppe and Pattaro, Cristian and Pearson, Daniel and Peden, John F and Pedersen, Nancy L and Pfeiffer, Andreas F H and Pichler, Irene and Polasek, Ozren and Posthuma, Danielle and Potter, Simon C and Pouta, Anneli and Province, Michael A and Rayner, Nigel W and Rice, Kenneth and Ripatti, Samuli and Rivadeneira, Fernando and Rolandsson, Olov and Sandbaek, Annelli and Sandhu, Manjinder and Sanna, Serena and Sayer, Avan Aihie and Scheet, Paul and Seedorf, Udo and Sharp, Stephen J and Shields, Beverley and Sigur{\dh}sson, Gunnar and Sijbrands, Eric J G and Silveira, Angela and Simpson, Laila and Singleton, Andrew and Smith, Nicholas L and Sovio, Ulla and Swift, Amy and Syddall, Holly and Syv{\"a}nen, Ann-Christine and T{\"o}njes, Anke and Uitterlinden, Andr{\'e} G and van Dijk, Ko Willems and Varma, Dhiraj and Visvikis-Siest, Sophie and Vitart, Veronique and Vogelzangs, Nicole and Waeber, G{\'e}rard and Wagner, Peter J and Walley, Andrew and Ward, Kim L and Watkins, Hugh and Wild, Sarah H and Willemsen, Gonneke and Witteman, Jaqueline C M and Yarnell, John W G and Zelenika, Diana and Zethelius, Bj{\"o}rn and Zhai, Guangju and Zhao, Jing Hua and Zillikens, M Carola and Borecki, Ingrid B and Meneton, Pierre and Magnusson, Patrik K E and Nathan, David M and Williams, Gordon H and Silander, Kaisa and Bornstein, Stefan R and Schwarz, Peter and Spranger, Joachim and Karpe, Fredrik and Shuldiner, Alan R and Cooper, Cyrus and Serrano-R{\'\i}os, Manuel and Lind, Lars and Palmer, Lyle J and Hu, Frank B and Franks, Paul W and Ebrahim, Shah and Marmot, Michael and Kao, W H Linda and Pramstaller, Peter Paul and Wright, Alan F and Stumvoll, Michael and Hamsten, Anders and Buchanan, Thomas A and Valle, Timo T and Rotter, Jerome I and Penninx, Brenda W J H and Boomsma, Dorret I and Cao, Antonio and Scuteri, Angelo and Schlessinger, David and Uda, Manuela and Ruokonen, Aimo and Jarvelin, Marjo-Riitta and Peltonen, Leena and Mooser, Vincent and Sladek, Robert and Musunuru, Kiran and Smith, Albert V and Edmondson, Andrew C and Stylianou, Ioannis M and Koseki, Masahiro and Pirruccello, James P and Chasman, Daniel I and Johansen, Christopher T and Fouchier, Sigrid W and Peloso, Gina M and Barbalic, Maja and Ricketts, Sally L and Bis, Joshua C and Feitosa, Mary F and Orho-Melander, Marju and Melander, Olle and Li, Xiaohui and Li, Mingyao and Cho, Yoon Shin and Go, Min Jin and Kim, Young Jin and Lee, Jong-Young and Park, Taesung and Kim, Kyunga and Sim, Xueling and Ong, Rick Twee-Hee and Croteau-Chonka, Damien C and Lange, Leslie A and Smith, Joshua D and Ziegler, Andreas and Zhang, Weihua and Zee, Robert Y L and Whitfield, John B and Thompson, John R and Surakka, Ida and Spector, Tim D and Smit, Johannes H and Sinisalo, Juha and Scott, James and Saharinen, Juha and Sabatti, Chiara and Rose, Lynda M and Roberts, Robert and Rieder, Mark and Parker, Alex N and Par{\'e}, Guillaume and O{\textquoteright}Donnell, Christopher J and Nieminen, Markku S and Nickerson, Deborah A and Montgomery, Grant W and McArdle, Wendy and Masson, David and Martin, Nicholas G and Marroni, Fabio and Lucas, Gavin and Luben, Robert and Lokki, Marja-Liisa and Lettre, Guillaume and Launer, Lenore J and Lakatta, Edward G and Laaksonen, Reijo and Kyvik, Kirsten O and K{\"o}nig, Inke R and Khaw, Kay-Tee and Kaplan, Lee M and Johansson, Asa and Janssens, A Cecile J W and Igl, Wilmar and Hovingh, G Kees and Hengstenberg, Christian and Havulinna, Aki S and Hastie, Nicholas D and Harris, Tamara B and Haritunians, Talin and Hall, Alistair S and Groop, Leif C and Gonzalez, Elena and Freimer, Nelson B and Erdmann, Jeanette and Ejebe, Kenechi G and D{\"o}ring, Angela and Dominiczak, Anna F and Demissie, Serkalem and Deloukas, Panagiotis and de Faire, Ulf and Crawford, Gabriel and Chen, Yii-der I and Caulfield, Mark J and Boekholdt, S Matthijs and Assimes, Themistocles L and Quertermous, Thomas and Seielstad, Mark and Wong, Tien Y and Tai, E-Shyong and Feranil, Alan B and Kuzawa, Christopher W and Taylor, Herman A and Gabriel, Stacey B and Holm, Hilma and Gudnason, Vilmundur and Krauss, Ronald M and Ordovas, Jose M and Munroe, Patricia B and Kooner, Jaspal S and Tall, Alan R and Hegele, Robert A and Kastelein, John J P and Schadt, Eric E and Strachan, David P and Reilly, Muredach P and Samani, Nilesh J and Schunkert, Heribert and Cupples, L Adrienne and Sandhu, Manjinder S and Ridker, Paul M and Rader, Daniel J and Kathiresan, Sekar} } @article {8014, title = {Common variants associated with plasma triglycerides and risk for coronary artery disease.}, journal = {Nat Genet}, volume = {45}, year = {2013}, month = {2013 Nov}, pages = {1345-52}, abstract = {

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 {\texttimes} 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism{\textquoteright}s effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

}, keywords = {Biological Transport, Cholesterol, HDL, Cholesterol, LDL, Coronary Artery Disease, Humans, Polymorphism, Single Nucleotide, Risk Factors, Triglycerides}, issn = {1546-1718}, doi = {10.1038/ng.2795}, author = {Do, Ron and Willer, Cristen J and Schmidt, Ellen M and Sengupta, Sebanti and Gao, Chi and Peloso, Gina M and Gustafsson, Stefan and Kanoni, Stavroula and Ganna, Andrea and Chen, Jin and Buchkovich, Martin L and Mora, Samia and Beckmann, Jacques S and Bragg-Gresham, Jennifer L and Chang, Hsing-Yi and Demirkan, Ayse and Den Hertog, Heleen M and Donnelly, Louise A and Ehret, Georg B and Esko, T{\~o}nu and Feitosa, Mary F and Ferreira, Teresa and Fischer, Krista and Fontanillas, Pierre and Fraser, Ross M and Freitag, Daniel F and Gurdasani, Deepti and Heikkil{\"a}, Kauko and Hypp{\"o}nen, Elina and Isaacs, Aaron and Jackson, Anne U and Johansson, Asa and Johnson, Toby and Kaakinen, Marika and Kettunen, Johannes and Kleber, Marcus E and Li, Xiaohui and Luan, Jian{\textquoteright}an and Lyytik{\"a}inen, Leo-Pekka and Magnusson, Patrik K E and Mangino, Massimo and Mihailov, Evelin and Montasser, May E and M{\"u}ller-Nurasyid, Martina and Nolte, Ilja M and O{\textquoteright}Connell, Jeffrey R and Palmer, Cameron D and Perola, Markus and Petersen, Ann-Kristin and Sanna, Serena and Saxena, Richa and Service, Susan K and Shah, Sonia and Shungin, Dmitry and Sidore, Carlo and Song, Ci and Strawbridge, Rona J and Surakka, Ida and Tanaka, Toshiko and Teslovich, Tanya M and Thorleifsson, Gudmar and van den Herik, Evita G and Voight, Benjamin F and Volcik, Kelly A and Waite, Lindsay L and Wong, Andrew and Wu, Ying and Zhang, Weihua and Absher, Devin and Asiki, Gershim and Barroso, In{\^e}s and Been, Latonya F and Bolton, Jennifer L and Bonnycastle, Lori L and Brambilla, Paolo and Burnett, Mary S and Cesana, Giancarlo and Dimitriou, Maria and Doney, Alex S F and D{\"o}ring, Angela and Elliott, Paul and Epstein, Stephen E and Eyjolfsson, Gudmundur Ingi and Gigante, Bruna and Goodarzi, Mark O and Grallert, Harald and Gravito, Martha L and Groves, Christopher J and Hallmans, G{\"o}ran and Hartikainen, Anna-Liisa and Hayward, Caroline and Hernandez, Dena and Hicks, Andrew A and Holm, Hilma and Hung, Yi-Jen and Illig, Thomas and Jones, Michelle R and Kaleebu, Pontiano and Kastelein, John J P and Khaw, Kay-Tee and Kim, Eric and Klopp, Norman and Komulainen, Pirjo and Kumari, Meena and Langenberg, Claudia and Lehtim{\"a}ki, Terho and Lin, Shih-Yi and Lindstr{\"o}m, Jaana and Loos, Ruth J F and Mach, Fran{\c c}ois and McArdle, Wendy L and Meisinger, Christa and Mitchell, Braxton D and M{\"u}ller, Gabrielle and Nagaraja, Ramaiah and Narisu, Narisu and Nieminen, Tuomo V M and Nsubuga, Rebecca N and Olafsson, Isleifur and Ong, Ken K and Palotie, Aarno and Papamarkou, Theodore and Pomilla, Cristina and Pouta, Anneli and Rader, Daniel J and Reilly, Muredach P and Ridker, Paul M and Rivadeneira, Fernando and Rudan, Igor and Ruokonen, Aimo and Samani, Nilesh and Scharnagl, Hubert and Seeley, Janet and Silander, Kaisa and Stan{\v c}{\'a}kov{\'a}, Alena and Stirrups, Kathleen and Swift, Amy J and Tiret, Laurence and Uitterlinden, Andr{\'e} G and van Pelt, L Joost and Vedantam, Sailaja and Wainwright, Nicholas and Wijmenga, Cisca and Wild, Sarah H and Willemsen, Gonneke and Wilsgaard, Tom and Wilson, James F and Young, Elizabeth H and Zhao, Jing Hua and Adair, Linda S and Arveiler, Dominique and Assimes, Themistocles L and Bandinelli, Stefania and Bennett, Franklyn and Bochud, Murielle and Boehm, Bernhard O and Boomsma, Dorret I and Borecki, Ingrid B and Bornstein, Stefan R and Bovet, Pascal and Burnier, Michel and Campbell, Harry and Chakravarti, Aravinda and Chambers, John C and Chen, Yii-Der Ida and Collins, Francis S and Cooper, Richard S and Danesh, John and Dedoussis, George and de Faire, Ulf and Feranil, Alan B and Ferrieres, Jean and Ferrucci, Luigi and Freimer, Nelson B and Gieger, Christian and Groop, Leif C and Gudnason, Vilmundur and Gyllensten, Ulf and Hamsten, Anders and Harris, Tamara B and Hingorani, Aroon and Hirschhorn, Joel N and Hofman, Albert and Hovingh, G Kees and Hsiung, Chao Agnes and Humphries, Steve E and Hunt, Steven C and Hveem, Kristian and Iribarren, Carlos and Jarvelin, Marjo-Riitta and Jula, Antti and K{\"a}h{\"o}nen, Mika and Kaprio, Jaakko and Kes{\"a}niemi, Antero and Kivimaki, Mika and Kooner, Jaspal S and Koudstaal, Peter J and Krauss, Ronald M and Kuh, Diana and Kuusisto, Johanna and Kyvik, Kirsten O and Laakso, Markku and Lakka, Timo A and Lind, Lars and Lindgren, Cecilia M and Martin, Nicholas G and M{\"a}rz, Winfried and McCarthy, Mark I and McKenzie, Colin A and Meneton, Pierre and Metspalu, Andres and Moilanen, Leena and Morris, Andrew D and Munroe, Patricia B and Nj{\o}lstad, Inger and Pedersen, Nancy L and Power, Chris and Pramstaller, Peter P and Price, Jackie F and Psaty, Bruce M and Quertermous, Thomas and Rauramaa, Rainer and Saleheen, Danish and Salomaa, Veikko and Sanghera, Dharambir K and Saramies, Jouko and Schwarz, Peter E H and Sheu, Wayne H-H and Shuldiner, Alan R and Siegbahn, Agneta and Spector, Tim D and Stefansson, Kari and Strachan, David P and Tayo, Bamidele O and Tremoli, Elena and Tuomilehto, Jaakko and Uusitupa, Matti and van Duijn, Cornelia M and Vollenweider, Peter and Wallentin, Lars and Wareham, Nicholas J and Whitfield, John B and Wolffenbuttel, Bruce H R and Altshuler, David and Ordovas, Jose M and Boerwinkle, Eric and Palmer, Colin N A and Thorsteinsdottir, Unnur and Chasman, Daniel I and Rotter, Jerome I and Franks, Paul W and Ripatti, Samuli and Cupples, L Adrienne and Sandhu, Manjinder S and Rich, Stephen S and Boehnke, Michael and Deloukas, Panos and Mohlke, Karen L and Ingelsson, Erik and Abecasis, Goncalo R and Daly, Mark J and Neale, Benjamin M and Kathiresan, Sekar} } @article {6154, title = {Discovery and refinement of loci associated with lipid levels.}, journal = {Nat Genet}, volume = {45}, year = {2013}, month = {2013 Nov}, pages = {1274-1283}, abstract = {

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 {\texttimes} 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

}, keywords = {African Continental Ancestry Group, Asian Continental Ancestry Group, Cholesterol, HDL, Cholesterol, LDL, Coronary Artery Disease, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Lipids, Triglycerides}, issn = {1546-1718}, doi = {10.1038/ng.2797}, author = {Willer, Cristen J and Schmidt, Ellen M and Sengupta, Sebanti and Peloso, Gina M and Gustafsson, Stefan and Kanoni, Stavroula and Ganna, Andrea and Chen, Jin and Buchkovich, Martin L and Mora, Samia and Beckmann, Jacques S and Bragg-Gresham, Jennifer L and Chang, Hsing-Yi and Demirkan, Ayse and Den Hertog, Heleen M and Do, Ron and Donnelly, Louise A and Ehret, Georg B and Esko, T{\~o}nu and Feitosa, Mary F and Ferreira, Teresa and Fischer, Krista and Fontanillas, Pierre and Fraser, Ross M and Freitag, Daniel F and Gurdasani, Deepti and Heikkil{\"a}, Kauko and Hypp{\"o}nen, Elina and Isaacs, Aaron and Jackson, Anne U and Johansson, Asa and Johnson, Toby and Kaakinen, Marika and Kettunen, Johannes and Kleber, Marcus E and Li, Xiaohui and Luan, Jian{\textquoteright}an and Lyytik{\"a}inen, Leo-Pekka and Magnusson, Patrik K E and Mangino, Massimo and Mihailov, Evelin and Montasser, May E and M{\"u}ller-Nurasyid, Martina and Nolte, Ilja M and O{\textquoteright}Connell, Jeffrey R and Palmer, Cameron D and Perola, Markus and Petersen, Ann-Kristin and Sanna, Serena and Saxena, Richa and Service, Susan K and Shah, Sonia and Shungin, Dmitry and Sidore, Carlo and Song, Ci and Strawbridge, Rona J and Surakka, Ida and Tanaka, Toshiko and Teslovich, Tanya M and Thorleifsson, Gudmar and van den Herik, Evita G and Voight, Benjamin F and Volcik, Kelly A and Waite, Lindsay L and Wong, Andrew and Wu, Ying and Zhang, Weihua and Absher, Devin and Asiki, Gershim and Barroso, In{\^e}s and Been, Latonya F and Bolton, Jennifer L and Bonnycastle, Lori L and Brambilla, Paolo and Burnett, Mary S and Cesana, Giancarlo and Dimitriou, Maria and Doney, Alex S F and D{\"o}ring, Angela and Elliott, Paul and Epstein, Stephen E and Ingi Eyjolfsson, Gudmundur and Gigante, Bruna and Goodarzi, Mark O and Grallert, Harald and Gravito, Martha L and Groves, Christopher J and Hallmans, G{\"o}ran and Hartikainen, Anna-Liisa and Hayward, Caroline and Hernandez, Dena and Hicks, Andrew A and Holm, Hilma and Hung, Yi-Jen and Illig, Thomas and Jones, Michelle R and Kaleebu, Pontiano and Kastelein, John J P and Khaw, Kay-Tee and Kim, Eric and Klopp, Norman and Komulainen, Pirjo and Kumari, Meena and Langenberg, Claudia and Lehtim{\"a}ki, Terho and Lin, Shih-Yi and Lindstr{\"o}m, Jaana and Loos, Ruth J F and Mach, Fran{\c c}ois and McArdle, Wendy L and Meisinger, Christa and Mitchell, Braxton D and M{\"u}ller, Gabrielle and Nagaraja, Ramaiah and Narisu, Narisu and Nieminen, Tuomo V M and Nsubuga, Rebecca N and Olafsson, Isleifur and Ong, Ken K and Palotie, Aarno and Papamarkou, Theodore and Pomilla, Cristina and Pouta, Anneli and Rader, Daniel J and Reilly, Muredach P and Ridker, Paul M and Rivadeneira, Fernando and Rudan, Igor and Ruokonen, Aimo and Samani, Nilesh and Scharnagl, Hubert and Seeley, Janet and Silander, Kaisa and Stan{\v c}{\'a}kov{\'a}, Alena and Stirrups, Kathleen and Swift, Amy J and Tiret, Laurence and Uitterlinden, Andr{\'e} G and van Pelt, L Joost and Vedantam, Sailaja and Wainwright, Nicholas and Wijmenga, Cisca and Wild, Sarah H and Willemsen, Gonneke and Wilsgaard, Tom and Wilson, James F and Young, Elizabeth H and Zhao, Jing Hua and Adair, Linda S and Arveiler, Dominique and Assimes, Themistocles L and Bandinelli, Stefania and Bennett, Franklyn and Bochud, Murielle and Boehm, Bernhard O and Boomsma, Dorret I and Borecki, Ingrid B and Bornstein, Stefan R and Bovet, Pascal and Burnier, Michel and Campbell, Harry and Chakravarti, Aravinda and Chambers, John C and Chen, Yii-Der Ida and Collins, Francis S and Cooper, Richard S and Danesh, John and Dedoussis, George and de Faire, Ulf and Feranil, Alan B and Ferrieres, Jean and Ferrucci, Luigi and Freimer, Nelson B and Gieger, Christian and Groop, Leif C and Gudnason, Vilmundur and Gyllensten, Ulf and Hamsten, Anders and Harris, Tamara B and Hingorani, Aroon and Hirschhorn, Joel N and Hofman, Albert and Hovingh, G Kees and Hsiung, Chao Agnes and Humphries, Steve E and Hunt, Steven C and Hveem, Kristian and Iribarren, Carlos and Jarvelin, Marjo-Riitta and Jula, Antti and K{\"a}h{\"o}nen, Mika and Kaprio, Jaakko and Kes{\"a}niemi, Antero and Kivimaki, Mika and Kooner, Jaspal S and Koudstaal, Peter J and Krauss, Ronald M and Kuh, Diana and Kuusisto, Johanna and Kyvik, Kirsten O and Laakso, Markku and Lakka, Timo A and Lind, Lars and Lindgren, Cecilia M and Martin, Nicholas G and M{\"a}rz, Winfried and McCarthy, Mark I and McKenzie, Colin A and Meneton, Pierre and Metspalu, Andres and Moilanen, Leena and Morris, Andrew D and Munroe, Patricia B and Nj{\o}lstad, Inger and Pedersen, Nancy L and Power, Chris and Pramstaller, Peter P and Price, Jackie F and Psaty, Bruce M and Quertermous, Thomas and Rauramaa, Rainer and Saleheen, Danish and Salomaa, Veikko and Sanghera, Dharambir K and Saramies, Jouko and Schwarz, Peter E H and Sheu, Wayne H-H and Shuldiner, Alan R and Siegbahn, Agneta and Spector, Tim D and Stefansson, Kari and Strachan, David P and Tayo, Bamidele O and Tremoli, Elena and Tuomilehto, Jaakko and Uusitupa, Matti and van Duijn, Cornelia M and Vollenweider, Peter and Wallentin, Lars and Wareham, Nicholas J and Whitfield, John B and Wolffenbuttel, Bruce H R and Ordovas, Jose M and Boerwinkle, Eric and Palmer, Colin N A and Thorsteinsdottir, Unnur and Chasman, Daniel I and Rotter, Jerome I and Franks, Paul W and Ripatti, Samuli and Cupples, L Adrienne and Sandhu, Manjinder S and Rich, Stephen S and Boehnke, Michael and Deloukas, Panos and Kathiresan, Sekar and Mohlke, Karen L and Ingelsson, Erik and Abecasis, Goncalo R} } @article {6027, title = {Genetic loci for retinal arteriolar microcirculation.}, journal = {PLoS One}, volume = {8}, year = {2013}, month = {2013}, pages = {e65804}, abstract = {

Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5{\texttimes}10(-8). This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11{\texttimes}10(-12) in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.

}, keywords = {Aged, Aged, 80 and over, Arterioles, Chromosomes, Human, Pair 5, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Male, MEF2 Transcription Factors, Microcirculation, Middle Aged, Models, Genetic, Retinal Vessels}, issn = {1932-6203}, doi = {10.1371/journal.pone.0065804}, author = {Sim, Xueling and Jensen, Richard A and Ikram, M Kamran and Cotch, Mary Frances and Li, Xiaohui and Macgregor, Stuart and Xie, Jing and Smith, Albert Vernon and Boerwinkle, Eric and Mitchell, Paul and Klein, Ronald and Klein, Barbara E K and Glazer, Nicole L and Lumley, Thomas and McKnight, Barbara and Psaty, Bruce M and de Jong, Paulus T V M and Hofman, Albert and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and van Duijn, Cornelia M and Aspelund, Thor and Eiriksdottir, Gudny and Harris, Tamara B and Jonasson, Fridbert and Launer, Lenore J and Attia, John and Baird, Paul N and Harrap, Stephen and Holliday, Elizabeth G and Inouye, Michael and Rochtchina, Elena and Scott, Rodney J and Viswanathan, Ananth and Li, Guo and Smith, Nicholas L and Wiggins, Kerri L and Kuo, Jane Z and Taylor, Kent D and Hewitt, Alex W and Martin, Nicholas G and Montgomery, Grant W and Sun, Cong and Young, Terri L and Mackey, David A and van Zuydam, Natalie R and Doney, Alex S F and Palmer, Colin N A and Morris, Andrew D and Rotter, Jerome I and Tai, E Shyong and Gudnason, Vilmundur and Vingerling, Johannes R and Siscovick, David S and Wang, Jie Jin and Wong, Tien Y} } @article {6075, title = {Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.}, journal = {Nat Genet}, volume = {45}, year = {2013}, month = {2013 Feb}, pages = {145-54}, abstract = {

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

}, keywords = {Analysis of Variance, European Continental Ancestry Group, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Glucose, Gout, Humans, Inhibins, Polymorphism, Single Nucleotide, Signal Transduction, Uric Acid}, issn = {1546-1718}, doi = {10.1038/ng.2500}, author = {K{\"o}ttgen, Anna and Albrecht, Eva and Teumer, Alexander and Vitart, Veronique and Krumsiek, Jan and Hundertmark, Claudia and Pistis, Giorgio and Ruggiero, Daniela and O{\textquoteright}Seaghdha, Conall M and Haller, Toomas and Yang, Qiong and Tanaka, Toshiko and Johnson, Andrew D and Kutalik, Zolt{\'a}n and Smith, Albert V and Shi, Julia and Struchalin, Maksim and Middelberg, Rita P S and Brown, Morris J and Gaffo, Angelo L and Pirastu, Nicola and Li, Guo and Hayward, Caroline and Zemunik, Tatijana and Huffman, Jennifer and Yengo, Loic and Zhao, Jing Hua and Demirkan, Ayse and Feitosa, Mary F and Liu, Xuan and Malerba, Giovanni and Lopez, Lorna M and van der Harst, Pim and Li, Xinzhong and Kleber, Marcus E and Hicks, Andrew A and Nolte, Ilja M and Johansson, Asa and Murgia, Federico and Wild, Sarah H and Bakker, Stephan J L and Peden, John F and Dehghan, Abbas and Steri, Maristella and Tenesa, Albert and Lagou, Vasiliki and Salo, Perttu and Mangino, Massimo and Rose, Lynda M and Lehtim{\"a}ki, Terho and Woodward, Owen M and Okada, Yukinori and Tin, Adrienne and M{\"u}ller, Christian and Oldmeadow, Christopher and Putku, Margus and Czamara, Darina and Kraft, Peter and Frogheri, Laura and Thun, Gian Andri and Grotevendt, Anne and Gislason, Gauti Kjartan and Harris, Tamara B and Launer, Lenore J and McArdle, Patrick and Shuldiner, Alan R and Boerwinkle, Eric and Coresh, Josef and Schmidt, Helena and Schallert, Michael and Martin, Nicholas G and Montgomery, Grant W and Kubo, Michiaki and Nakamura, Yusuke and Tanaka, Toshihiro and Munroe, Patricia B and Samani, Nilesh J and Jacobs, David R and Liu, Kiang and D{\textquoteright}Adamo, Pio and Ulivi, Sheila and Rotter, Jerome I and Psaty, Bruce M and Vollenweider, Peter and Waeber, G{\'e}rard and Campbell, Susan and Devuyst, Olivier and Navarro, Pau and Kolcic, Ivana and Hastie, Nicholas and Balkau, Beverley and Froguel, Philippe and Esko, T{\~o}nu and Salumets, Andres and Khaw, Kay Tee and Langenberg, Claudia and Wareham, Nicholas J and Isaacs, Aaron and Kraja, Aldi and Zhang, Qunyuan and Wild, Philipp S and Scott, Rodney J and Holliday, Elizabeth G and Org, Elin and Viigimaa, Margus and Bandinelli, Stefania and Metter, Jeffrey E and Lupo, Antonio and Trabetti, Elisabetta and Sorice, Rossella and D{\"o}ring, Angela and Lattka, Eva and Strauch, Konstantin and Theis, Fabian and Waldenberger, Melanie and Wichmann, H-Erich and Davies, Gail and Gow, Alan J and Bruinenberg, Marcel and Stolk, Ronald P and Kooner, Jaspal S and Zhang, Weihua and Winkelmann, Bernhard R and Boehm, Bernhard O and Lucae, Susanne and Penninx, Brenda W and Smit, Johannes H and Curhan, Gary and Mudgal, Poorva and Plenge, Robert M and Portas, Laura and Persico, Ivana and Kirin, Mirna and Wilson, James F and Mateo Leach, Irene and van Gilst, Wiek H and Goel, Anuj and Ongen, Halit and Hofman, Albert and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Imboden, Medea and von Eckardstein, Arnold and Cucca, Francesco and Nagaraja, Ramaiah and Piras, Maria Grazia and Nauck, Matthias and Schurmann, Claudia and Budde, Kathrin and Ernst, Florian and Farrington, Susan M and Theodoratou, Evropi and Prokopenko, Inga and Stumvoll, Michael and Jula, Antti and Perola, Markus and Salomaa, Veikko and Shin, So-Youn and Spector, Tim D and Sala, Cinzia and Ridker, Paul M and K{\"a}h{\"o}nen, Mika and Viikari, Jorma and Hengstenberg, Christian and Nelson, Christopher P and Meschia, James F and Nalls, Michael A and Sharma, Pankaj and Singleton, Andrew B and Kamatani, Naoyuki and Zeller, Tanja and Burnier, Michel and Attia, John and Laan, Maris and Klopp, Norman and Hillege, Hans L and Kloiber, Stefan and Choi, Hyon and Pirastu, Mario and Tore, Silvia and Probst-Hensch, Nicole M and V{\"o}lzke, Henry and Gudnason, Vilmundur and Parsa, Afshin and Schmidt, Reinhold and Whitfield, John B and Fornage, Myriam and Gasparini, Paolo and Siscovick, David S and Polasek, Ozren and Campbell, Harry and Rudan, Igor and Bouatia-Naji, Nabila and Metspalu, Andres and Loos, Ruth J F and van Duijn, Cornelia M and Borecki, Ingrid B and Ferrucci, Luigi and Gambaro, Giovanni and Deary, Ian J and Wolffenbuttel, Bruce H R and Chambers, John C and M{\"a}rz, Winfried and Pramstaller, Peter P and Snieder, Harold and Gyllensten, Ulf and Wright, Alan F and Navis, Gerjan and Watkins, Hugh and Witteman, Jacqueline C M and Sanna, Serena and Schipf, Sabine and Dunlop, Malcolm G and T{\"o}njes, Anke and Ripatti, Samuli and Soranzo, Nicole and Toniolo, Daniela and Chasman, Daniel I and Raitakari, Olli and Kao, W H Linda and Ciullo, Marina and Fox, Caroline S and Caulfield, Mark and Bochud, Murielle and Gieger, Christian} } @article {6152, title = {Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.}, journal = {Nat Genet}, volume = {45}, year = {2013}, month = {2013 May}, pages = {501-12}, abstract = {

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

}, keywords = {Anthropometry, Body Height, Body Mass Index, Case-Control Studies, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Meta-Analysis as Topic, Obesity, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Waist-Hip Ratio}, issn = {1546-1718}, doi = {10.1038/ng.2606}, author = {Berndt, Sonja I and Gustafsson, Stefan and M{\"a}gi, Reedik and Ganna, Andrea and Wheeler, Eleanor and Feitosa, Mary F and Justice, Anne E and Monda, Keri L and Croteau-Chonka, Damien C and Day, Felix R and Esko, T{\~o}nu and Fall, Tove and Ferreira, Teresa and Gentilini, Davide and Jackson, Anne U and Luan, Jian{\textquoteright}an and Randall, Joshua C and Vedantam, Sailaja and Willer, Cristen J and Winkler, Thomas W and Wood, Andrew R and Workalemahu, Tsegaselassie and Hu, Yi-Juan and Lee, Sang Hong and Liang, Liming and Lin, Dan-Yu and Min, Josine L and Neale, Benjamin M and Thorleifsson, Gudmar and Yang, Jian and Albrecht, Eva and Amin, Najaf and Bragg-Gresham, Jennifer L and Cadby, Gemma and den Heijer, Martin and Eklund, Niina and Fischer, Krista and Goel, Anuj and Hottenga, Jouke-Jan and Huffman, Jennifer E and Jarick, Ivonne and Johansson, Asa and Johnson, Toby and Kanoni, Stavroula and Kleber, Marcus E and K{\"o}nig, Inke R and Kristiansson, Kati and Kutalik, Zolt{\'a}n and Lamina, Claudia and Lecoeur, C{\'e}cile and Li, Guo and Mangino, Massimo and McArdle, Wendy L and Medina-G{\'o}mez, Carolina and M{\"u}ller-Nurasyid, Martina and Ngwa, Julius S and Nolte, Ilja M and Paternoster, Lavinia and Pechlivanis, Sonali and Perola, Markus and Peters, Marjolein J and Preuss, Michael and Rose, Lynda M and Shi, Jianxin and Shungin, Dmitry and Smith, Albert Vernon and Strawbridge, Rona J and Surakka, Ida and Teumer, Alexander and Trip, Mieke D and Tyrer, Jonathan and van Vliet-Ostaptchouk, Jana V and Vandenput, Liesbeth and Waite, Lindsay L and Zhao, Jing Hua and Absher, Devin and Asselbergs, Folkert W and Atalay, Mustafa and Attwood, Antony P and Balmforth, Anthony J and Basart, Hanneke and Beilby, John and Bonnycastle, Lori L and Brambilla, Paolo and Bruinenberg, Marcel and Campbell, Harry and Chasman, Daniel I and Chines, Peter S and Collins, Francis S and Connell, John M and Cookson, William O and de Faire, Ulf and de Vegt, Femmie and Dei, Mariano and Dimitriou, Maria and Edkins, Sarah and Estrada, Karol and Evans, David M and Farrall, Martin and Ferrario, Marco M and Ferrieres, Jean and Franke, Lude and Frau, Francesca and Gejman, Pablo V and Grallert, Harald and Gr{\"o}nberg, Henrik and Gudnason, Vilmundur and Hall, Alistair S and Hall, Per and Hartikainen, Anna-Liisa and Hayward, Caroline and Heard-Costa, Nancy L and Heath, Andrew C and Hebebrand, Johannes and Homuth, Georg and Hu, Frank B and Hunt, Sarah E and Hypp{\"o}nen, Elina and Iribarren, Carlos and Jacobs, Kevin B and Jansson, John-Olov and Jula, Antti and K{\"a}h{\"o}nen, Mika and Kathiresan, Sekar and Kee, Frank and Khaw, Kay-Tee and Kivimaki, Mika and Koenig, Wolfgang and Kraja, Aldi T and Kumari, Meena and Kuulasmaa, Kari and Kuusisto, Johanna and Laitinen, Jaana H and Lakka, Timo A and Langenberg, Claudia and Launer, Lenore J and Lind, Lars and Lindstr{\"o}m, Jaana and Liu, Jianjun and Liuzzi, Antonio and Lokki, Marja-Liisa and Lorentzon, Mattias and Madden, Pamela A and Magnusson, Patrik K and Manunta, Paolo and Marek, Diana and M{\"a}rz, Winfried and Mateo Leach, Irene and McKnight, Barbara and Medland, Sarah E and Mihailov, Evelin and Milani, Lili and Montgomery, Grant W and Mooser, Vincent and M{\"u}hleisen, Thomas W and Munroe, Patricia B and Musk, Arthur W and Narisu, Narisu and Navis, Gerjan and Nicholson, George and Nohr, Ellen A and Ong, Ken K and Oostra, Ben A and Palmer, Colin N A and Palotie, Aarno and Peden, John F and Pedersen, Nancy and Peters, Annette and Polasek, Ozren and Pouta, Anneli and Pramstaller, Peter P and Prokopenko, Inga and P{\"u}tter, Carolin and Radhakrishnan, Aparna and Raitakari, Olli and Rendon, Augusto and Rivadeneira, Fernando and Rudan, Igor and Saaristo, Timo E and Sambrook, Jennifer G and Sanders, Alan R and Sanna, Serena and Saramies, Jouko and Schipf, Sabine and Schreiber, Stefan and Schunkert, Heribert and Shin, So-Youn and Signorini, Stefano and Sinisalo, Juha and Skrobek, Boris and Soranzo, Nicole and Stan{\v c}{\'a}kov{\'a}, Alena and Stark, Klaus and Stephens, Jonathan C and Stirrups, Kathleen and Stolk, Ronald P and Stumvoll, Michael and Swift, Amy J and Theodoraki, Eirini V and Thorand, Barbara and Tr{\'e}gou{\"e}t, David-Alexandre and Tremoli, Elena and van der Klauw, Melanie M and van Meurs, Joyce B J and Vermeulen, Sita H and Viikari, Jorma and Virtamo, Jarmo and Vitart, Veronique and Waeber, G{\'e}rard and Wang, Zhaoming and Widen, Elisabeth and Wild, Sarah H and Willemsen, Gonneke and Winkelmann, Bernhard R and Witteman, Jacqueline C M and Wolffenbuttel, Bruce H R and Wong, Andrew and Wright, Alan F and Zillikens, M Carola and Amouyel, Philippe and Boehm, Bernhard O and Boerwinkle, Eric and Boomsma, Dorret I and Caulfield, Mark J and Chanock, Stephen J and Cupples, L Adrienne and Cusi, Daniele and Dedoussis, George V and Erdmann, Jeanette and Eriksson, Johan G and Franks, Paul W and Froguel, Philippe and Gieger, Christian and Gyllensten, Ulf and Hamsten, Anders and Harris, Tamara B and Hengstenberg, Christian and Hicks, Andrew A and Hingorani, Aroon and Hinney, Anke and Hofman, Albert and Hovingh, Kees G and Hveem, Kristian and Illig, Thomas and Jarvelin, Marjo-Riitta and J{\"o}ckel, Karl-Heinz and Keinanen-Kiukaanniemi, Sirkka M and Kiemeney, Lambertus A and Kuh, Diana and Laakso, Markku and Lehtim{\"a}ki, Terho and Levinson, Douglas F and Martin, Nicholas G and Metspalu, Andres and Morris, Andrew D and Nieminen, Markku S and Nj{\o}lstad, Inger and Ohlsson, Claes and Oldehinkel, Albertine J and Ouwehand, Willem H and Palmer, Lyle J and Penninx, Brenda and Power, Chris and Province, Michael A and Psaty, Bruce M and Qi, Lu and Rauramaa, Rainer and Ridker, Paul M and Ripatti, Samuli and Salomaa, Veikko and Samani, Nilesh J and Snieder, Harold and S{\o}rensen, Thorkild I A and Spector, Timothy D and Stefansson, Kari and T{\"o}njes, Anke and Tuomilehto, Jaakko and Uitterlinden, Andr{\'e} G and Uusitupa, Matti and van der Harst, Pim and Vollenweider, Peter and Wallaschofski, Henri and Wareham, Nicholas J and Watkins, Hugh and Wichmann, H-Erich and Wilson, James F and Abecasis, Goncalo R and Assimes, Themistocles L and Barroso, In{\^e}s and Boehnke, Michael and Borecki, Ingrid B and Deloukas, Panos and Fox, Caroline S and Frayling, Timothy and Groop, Leif C and Haritunian, Talin and Heid, Iris M and Hunter, David and Kaplan, Robert C and Karpe, Fredrik and Moffatt, Miriam F and Mohlke, Karen L and O{\textquoteright}Connell, Jeffrey R and Pawitan, Yudi and Schadt, Eric E and Schlessinger, David and Steinthorsdottir, Valgerdur and Strachan, David P and Thorsteinsdottir, Unnur and van Duijn, Cornelia M and Visscher, Peter M and Di Blasio, Anna Maria and Hirschhorn, Joel N and Lindgren, Cecilia M and Morris, Andrew P and Meyre, David and Scherag, Andre and McCarthy, Mark I and Speliotes, Elizabeth K and North, Kari E and Loos, Ruth J F and Ingelsson, Erik} } @article {8015, title = {Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.}, journal = {Nat Genet}, volume = {45}, year = {2013}, month = {2013 Jun}, pages = {621-31}, abstract = {

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

}, keywords = {Animals, Arrhythmias, Cardiac, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Heart Conduction System, Heart Rate, Humans, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Quantitative Trait Loci}, issn = {1546-1718}, doi = {10.1038/ng.2610}, author = {den Hoed, Marcel and Eijgelsheim, Mark and Esko, T{\~o}nu and Brundel, Bianca J J M and Peal, David S and Evans, David M and Nolte, Ilja M and Segr{\`e}, Ayellet V and Holm, Hilma and Handsaker, Robert E and Westra, Harm-Jan and Johnson, Toby and Isaacs, Aaron and Yang, Jian and Lundby, Alicia and Zhao, Jing Hua and Kim, Young Jin and Go, Min Jin and Almgren, Peter and Bochud, Murielle and Boucher, Gabrielle and Cornelis, Marilyn C and Gudbjartsson, Daniel and Hadley, David and van der Harst, Pim and Hayward, Caroline and den Heijer, Martin and Igl, Wilmar and Jackson, Anne U and Kutalik, Zolt{\'a}n and Luan, Jian{\textquoteright}an and Kemp, John P and Kristiansson, Kati and Ladenvall, Claes and Lorentzon, Mattias and Montasser, May E and Njajou, Omer T and O{\textquoteright}Reilly, Paul F and Padmanabhan, Sandosh and St Pourcain, Beate and Rankinen, Tuomo and Salo, Perttu and Tanaka, Toshiko and Timpson, Nicholas J and Vitart, Veronique and Waite, Lindsay and Wheeler, William and Zhang, Weihua and Draisma, Harmen H M and Feitosa, Mary F and Kerr, Kathleen F and Lind, Penelope A and Mihailov, Evelin and Onland-Moret, N Charlotte and Song, Ci and Weedon, Michael N and Xie, Weijia and Yengo, Loic and Absher, Devin and Albert, Christine M and Alonso, Alvaro and Arking, Dan E and de Bakker, Paul I W and Balkau, Beverley and Barlassina, Cristina and Benaglio, Paola and Bis, Joshua C and Bouatia-Naji, Nabila and Brage, S{\o}ren and Chanock, Stephen J and Chines, Peter S and Chung, Mina and Darbar, Dawood and Dina, Christian and D{\"o}rr, Marcus and Elliott, Paul and Felix, Stephan B and Fischer, Krista and Fuchsberger, Christian and de Geus, Eco J C and Goyette, Philippe and Gudnason, Vilmundur and Harris, Tamara B and Hartikainen, Anna-Liisa and Havulinna, Aki S and Heckbert, Susan R and Hicks, Andrew A and Hofman, Albert and Holewijn, Suzanne and Hoogstra-Berends, Femke and Hottenga, Jouke-Jan and Jensen, Majken K and Johansson, Asa and Junttila, Juhani and K{\"a}{\"a}b, Stefan and Kanon, Bart and Ketkar, Shamika and Khaw, Kay-Tee and Knowles, Joshua W and Kooner, Angrad S and Kors, Jan A and Kumari, Meena and Milani, Lili and Laiho, P{\"a}ivi and Lakatta, Edward G and Langenberg, Claudia and Leusink, Maarten and Liu, Yongmei and Luben, Robert N and Lunetta, Kathryn L and Lynch, Stacey N and Markus, Marcello R P and Marques-Vidal, Pedro and Mateo Leach, Irene and McArdle, Wendy L and McCarroll, Steven A and Medland, Sarah E and Miller, Kathryn A and Montgomery, Grant W and Morrison, Alanna C and M{\"u}ller-Nurasyid, Martina and Navarro, Pau and Nelis, Mari and O{\textquoteright}Connell, Jeffrey R and O{\textquoteright}Donnell, Christopher J and Ong, Ken K and Newman, Anne B and Peters, Annette and Polasek, Ozren and Pouta, Anneli and Pramstaller, Peter P and Psaty, Bruce M and Rao, Dabeeru C and Ring, Susan M and Rossin, Elizabeth J and Rudan, Diana and Sanna, Serena and Scott, Robert A and Sehmi, Jaban S and Sharp, Stephen and Shin, Jordan T and Singleton, Andrew B and Smith, Albert V and Soranzo, Nicole and Spector, Tim D and Stewart, Chip and Stringham, Heather M and Tarasov, Kirill V and Uitterlinden, Andr{\'e} G and Vandenput, Liesbeth and Hwang, Shih-Jen and Whitfield, John B and Wijmenga, Cisca and Wild, Sarah H and Willemsen, Gonneke and Wilson, James F and Witteman, Jacqueline C M and Wong, Andrew and Wong, Quenna and Jamshidi, Yalda and Zitting, Paavo and Boer, Jolanda M A and Boomsma, Dorret I and Borecki, Ingrid B and van Duijn, Cornelia M and Ekelund, Ulf and Forouhi, Nita G and Froguel, Philippe and Hingorani, Aroon and Ingelsson, Erik and Kivimaki, Mika and Kronmal, Richard A and Kuh, Diana and Lind, Lars and Martin, Nicholas G and Oostra, Ben A and Pedersen, Nancy L and Quertermous, Thomas and Rotter, Jerome I and van der Schouw, Yvonne T and Verschuren, W M Monique and Walker, Mark and Albanes, Demetrius and Arnar, David O and Assimes, Themistocles L and Bandinelli, Stefania and Boehnke, Michael and de Boer, Rudolf A and Bouchard, Claude and Caulfield, W L Mark and Chambers, John C and Curhan, Gary and Cusi, Daniele and Eriksson, Johan and Ferrucci, Luigi and van Gilst, Wiek H and Glorioso, Nicola and de Graaf, Jacqueline and Groop, Leif and Gyllensten, Ulf and Hsueh, Wen-Chi and Hu, Frank B and Huikuri, Heikki V and Hunter, David J and Iribarren, Carlos and Isomaa, Bo and Jarvelin, Marjo-Riitta and Jula, Antti and K{\"a}h{\"o}nen, Mika and Kiemeney, Lambertus A and van der Klauw, Melanie M and Kooner, Jaspal S and Kraft, Peter and Iacoviello, Licia and Lehtim{\"a}ki, Terho and Lokki, Marja-Liisa L and Mitchell, Braxton D and Navis, Gerjan and Nieminen, Markku S and Ohlsson, Claes and Poulter, Neil R and Qi, Lu and Raitakari, Olli T and Rimm, Eric B and Rioux, John D and Rizzi, Federica and Rudan, Igor and Salomaa, Veikko and Sever, Peter S and Shields, Denis C and Shuldiner, Alan R and Sinisalo, Juha and Stanton, Alice V and Stolk, Ronald P and Strachan, David P and Tardif, Jean-Claude and Thorsteinsdottir, Unnur and Tuomilehto, Jaako and van Veldhuisen, Dirk J and Virtamo, Jarmo and Viikari, Jorma and Vollenweider, Peter and Waeber, G{\'e}rard and Widen, Elisabeth and Cho, Yoon Shin and Olsen, Jesper V and Visscher, Peter M and Willer, Cristen and Franke, Lude and Erdmann, Jeanette and Thompson, John R and Pfeufer, Arne and Sotoodehnia, Nona and Newton-Cheh, Christopher and Ellinor, Patrick T and Stricker, Bruno H Ch and Metspalu, Andres and Perola, Markus and Beckmann, Jacques S and Smith, George Davey and Stefansson, Kari and Wareham, Nicholas J and Munroe, Patricia B and Sibon, Ody C M and Milan, David J and Snieder, Harold and Samani, Nilesh J and Loos, Ruth J F} } @article {6028, title = {Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.}, journal = {PLoS Genet}, volume = {9}, year = {2013}, month = {2013 Jun}, pages = {e1003500}, abstract = {

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5\%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5{\texttimes}10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

}, keywords = {Anthropometry, Body Height, Body Mass Index, Body Weight, Body Weights and Measures, Female, Genetic Loci, Genome, Human, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Sex Characteristics, Waist Circumference, Waist-Hip Ratio}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003500}, author = {Randall, Joshua C and Winkler, Thomas W and Kutalik, Zolt{\'a}n and Berndt, Sonja I and Jackson, Anne U and Monda, Keri L and Kilpel{\"a}inen, Tuomas O and Esko, T{\~o}nu and M{\"a}gi, Reedik and Li, Shengxu and Workalemahu, Tsegaselassie and Feitosa, Mary F and Croteau-Chonka, Damien C and Day, Felix R and Fall, Tove and Ferreira, Teresa and Gustafsson, Stefan and Locke, Adam E and Mathieson, Iain and Scherag, Andre and Vedantam, Sailaja and Wood, Andrew R and Liang, Liming and Steinthorsdottir, Valgerdur and Thorleifsson, Gudmar and Dermitzakis, Emmanouil T and Dimas, Antigone S and Karpe, Fredrik and Min, Josine L and Nicholson, George and Clegg, Deborah J and Person, Thomas and Krohn, Jon P and Bauer, Sabrina and Buechler, Christa and Eisinger, Kristina and Bonnefond, Am{\'e}lie and Froguel, Philippe and Hottenga, Jouke-Jan and Prokopenko, Inga and Waite, Lindsay L and Harris, Tamara B and Smith, Albert Vernon and Shuldiner, Alan R and McArdle, Wendy L and Caulfield, Mark J and Munroe, Patricia B and Gr{\"o}nberg, Henrik and Chen, Yii-Der Ida and Li, Guo and Beckmann, Jacques S and Johnson, Toby and Thorsteinsdottir, Unnur and Teder-Laving, Maris and Khaw, Kay-Tee and Wareham, Nicholas J and Zhao, Jing Hua and Amin, Najaf and Oostra, Ben A and Kraja, Aldi T and Province, Michael A and Cupples, L Adrienne and Heard-Costa, Nancy L and Kaprio, Jaakko and Ripatti, Samuli and Surakka, Ida and Collins, Francis S and Saramies, Jouko and Tuomilehto, Jaakko and Jula, Antti and Salomaa, Veikko and Erdmann, Jeanette and Hengstenberg, Christian and Loley, Christina and Schunkert, Heribert and Lamina, Claudia and Wichmann, H Erich and Albrecht, Eva and Gieger, Christian and Hicks, Andrew A and Johansson, Asa and Pramstaller, Peter P and Kathiresan, Sekar and Speliotes, Elizabeth K and Penninx, Brenda and Hartikainen, Anna-Liisa and Jarvelin, Marjo-Riitta and Gyllensten, Ulf and Boomsma, Dorret I and Campbell, Harry and Wilson, James F and Chanock, Stephen J and Farrall, Martin and Goel, Anuj and Medina-G{\'o}mez, Carolina and Rivadeneira, Fernando and Estrada, Karol and Uitterlinden, Andr{\'e} G and Hofman, Albert and Zillikens, M Carola and den Heijer, Martin and Kiemeney, Lambertus A and Maschio, Andrea and Hall, Per and Tyrer, Jonathan and Teumer, Alexander and V{\"o}lzke, Henry and Kovacs, Peter and T{\"o}njes, Anke and Mangino, Massimo and Spector, Tim D and Hayward, Caroline and Rudan, Igor and Hall, Alistair S and Samani, Nilesh J and Attwood, Antony Paul and Sambrook, Jennifer G and Hung, Joseph and Palmer, Lyle J and Lokki, Marja-Liisa and Sinisalo, Juha and Boucher, Gabrielle and Huikuri, Heikki and Lorentzon, Mattias and Ohlsson, Claes and Eklund, Niina and Eriksson, Johan G and Barlassina, Cristina and Rivolta, Carlo and Nolte, Ilja M and Snieder, Harold and van der Klauw, Melanie M and van Vliet-Ostaptchouk, Jana V and Gejman, Pablo V and Shi, Jianxin and Jacobs, Kevin B and Wang, Zhaoming and Bakker, Stephan J L and Mateo Leach, Irene and Navis, Gerjan and van der Harst, Pim and Martin, Nicholas G and Medland, Sarah E and Montgomery, Grant W and Yang, Jian and Chasman, Daniel I and Ridker, Paul M and Rose, Lynda M and Lehtim{\"a}ki, Terho and Raitakari, Olli and Absher, Devin and Iribarren, Carlos and Basart, Hanneke and Hovingh, Kees G and Hypp{\"o}nen, Elina and Power, Chris and Anderson, Denise and Beilby, John P and Hui, Jennie and Jolley, Jennifer and Sager, Hendrik and Bornstein, Stefan R and Schwarz, Peter E H and Kristiansson, Kati and Perola, Markus and Lindstr{\"o}m, Jaana and Swift, Amy J and Uusitupa, Matti and Atalay, Mustafa and Lakka, Timo A and Rauramaa, Rainer and Bolton, Jennifer L and Fowkes, Gerry and Fraser, Ross M and Price, Jackie F and Fischer, Krista and Krjut{\r a} Kov, Kaarel and Metspalu, Andres and Mihailov, Evelin and Langenberg, Claudia and Luan, Jian{\textquoteright}an and Ong, Ken K and Chines, Peter S and Keinanen-Kiukaanniemi, Sirkka M and Saaristo, Timo E and Edkins, Sarah and Franks, Paul W and Hallmans, G{\"o}ran and Shungin, Dmitry and Morris, Andrew David and Palmer, Colin N A and Erbel, Raimund and Moebus, Susanne and N{\"o}then, Markus M and Pechlivanis, Sonali and Hveem, Kristian and Narisu, Narisu and Hamsten, Anders and Humphries, Steve E and Strawbridge, Rona J and Tremoli, Elena and Grallert, Harald and Thorand, Barbara and Illig, Thomas and Koenig, Wolfgang and M{\"u}ller-Nurasyid, Martina and Peters, Annette and Boehm, Bernhard O and Kleber, Marcus E and M{\"a}rz, Winfried and Winkelmann, Bernhard R and Kuusisto, Johanna and Laakso, Markku and Arveiler, Dominique and Cesana, Giancarlo and Kuulasmaa, Kari and Virtamo, Jarmo and Yarnell, John W G and Kuh, Diana and Wong, Andrew and Lind, Lars and de Faire, Ulf and Gigante, Bruna and Magnusson, Patrik K E and Pedersen, Nancy L and Dedoussis, George and Dimitriou, Maria and Kolovou, Genovefa and Kanoni, Stavroula and Stirrups, Kathleen and Bonnycastle, Lori L and Nj{\o}lstad, Inger and Wilsgaard, Tom and Ganna, Andrea and Rehnberg, Emil and Hingorani, Aroon and Kivimaki, Mika and Kumari, Meena and Assimes, Themistocles L and Barroso, In{\^e}s and Boehnke, Michael and Borecki, Ingrid B and Deloukas, Panos and Fox, Caroline S and Frayling, Timothy and Groop, Leif C and Haritunians, Talin and Hunter, David and Ingelsson, Erik and Kaplan, Robert and Mohlke, Karen L and O{\textquoteright}Connell, Jeffrey R and Schlessinger, David and Strachan, David P and Stefansson, Kari and van Duijn, Cornelia M and Abecasis, Goncalo R and McCarthy, Mark I and Hirschhorn, Joel N and Qi, Lu and Loos, Ruth J F and Lindgren, Cecilia M and North, Kari E and Heid, Iris M} } @article {6817, title = {DCAF4, a novel gene associated with leucocyte telomere length.}, journal = {J Med Genet}, volume = {52}, year = {2015}, month = {2015 Mar}, pages = {157-62}, abstract = {

BACKGROUND: Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether DCAF4 (DDB1 and CUL4-associated factor 4) is associated with LTL. In addition, using ingenuity pathway analysis (IPA), we examined whether LTL-associated genes in the general population might partially explain the inherently longer LTL in patients with sporadic melanoma, the risk for which is increased with ultraviolet radiation (UVR).

RESULTS: Genome-wide association (GWA) meta-analysis and de novo genotyping of 20 022 individuals revealed a novel association (p=6.4{\texttimes}10(-10)) between LTL and rs2535913, which lies within DCAF4. Notably, eQTL analysis showed that rs2535913 is associated with decline in DCAF4 expressions in both lymphoblastoid cells and sun-exposed skin (p=4.1{\texttimes}10(-3) and 2{\texttimes}10(-3), respectively). Moreover, IPA revealed that LTL-associated genes, derived from GWA meta-analysis (N=9190), are over-represented among genes engaged in melanoma pathways. Meeting increasingly stringent p value thresholds (p<0.05, <0.01, <0.005, <0.001) in the LTL-GWA meta-analysis, these genes were jointly over-represented for melanoma at p values ranging from 1.97{\texttimes}10(-169) to 3.42{\texttimes}10(-24).

CONCLUSIONS: We uncovered a new locus associated with LTL in the general population. We also provided preliminary findings that suggest a link of LTL through genetic mechanisms with UVR and melanoma in the general population.

}, keywords = {Alleles, Carrier Proteins, Gene Expression Regulation, Genome-Wide Association Study, Humans, Leukocytes, Melanoma, Risk Factors, Telomere, Telomere Homeostasis}, issn = {1468-6244}, doi = {10.1136/jmedgenet-2014-102681}, author = {Mangino, Massimo and Christiansen, Lene and Stone, Rivka and Hunt, Steven C and Horvath, Kent and Eisenberg, Dan T A and Kimura, Masayuki and Petersen, Inge and Kark, Jeremy D and Herbig, Utz and Reiner, Alex P and Benetos, Athanase and Codd, Veryan and Nyholt, Dale R and Sinnreich, Ronit and Christensen, Kaare and Nassar, Hisham and Hwang, Shih-Jen and Levy, Daniel and Bataille, Veronique and Fitzpatrick, Annette L and Chen, Wei and Berenson, Gerald S and Samani, Nilesh J and Martin, Nicholas G and Tishkoff, Sarah and Schork, Nicholas J and Kyvik, Kirsten Ohm and Dalg{\r a}rd, Christine and Spector, Timothy D and Aviv, Abraham} } @article {7168, title = {Genetic variants in RBFOX3 are associated with sleep latency.}, journal = {Eur J Hum Genet}, volume = {24}, year = {2016}, month = {2016 Oct}, pages = {1488-95}, abstract = {

Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta-analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P-values=5.77 {\texttimes} 10(-08), 6.59 {\texttimes} 10(-)(08) and 9.17 {\texttimes} 10(-)(08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 {\texttimes} 10(-)(02), 7.0 {\texttimes} 10(-)(03) and 2.5 {\texttimes} 10(-)(03); combined meta-analysis P-values=5.5 {\texttimes} 10(-07), 5.4 {\texttimes} 10(-07) and 1.0 {\texttimes} 10(-07)). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 {\texttimes} 10(-316)) and the central nervous system (P-value=7.5 {\texttimes} 10(-)(321)). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values<2.9 {\texttimes} 10(-11)) that are crucial in triggering the onset of sleep. To conclude, in this first large-scale GWAS of sleep latency we report a novel association of variants in RBFOX3 gene. Further, a functional prediction of RBFOX3 supports the involvement of RBFOX3 with sleep latency.

}, issn = {1476-5438}, doi = {10.1038/ejhg.2016.31}, author = {Amin, Najaf and Allebrandt, Karla V and van der Spek, Ashley and M{\"u}ller-Myhsok, Bertram and Hek, Karin and Teder-Laving, Maris and Hayward, Caroline and Esko, T{\~o}nu and van Mill, Josine G and Mbarek, Hamdi and Watson, Nathaniel F and Melville, Scott A and Del Greco, Fabiola M and Byrne, Enda M and Oole, Edwin and Kolcic, Ivana and Chen, Ting-Hsu and Evans, Daniel S and Coresh, Josef and Vogelzangs, Nicole and Karjalainen, Juha and Willemsen, Gonneke and Gharib, Sina A and Zgaga, Lina and Mihailov, Evelin and Stone, Katie L and Campbell, Harry and Brouwer, Rutger Ww and Demirkan, Ayse and Isaacs, Aaron and Dogas, Zoran and Marciante, Kristin D and Campbell, Susan and Borovecki, Fran and Luik, Annemarie I and Li, Man and Hottenga, Jouke Jan and Huffman, Jennifer E and van den Hout, Mirjam Cgn and Cummings, Steven R and Aulchenko, Yurii S and Gehrman, Philip R and Uitterlinden, Andr{\'e} G and Wichmann, Heinz-Erich and M{\"u}ller-Nurasyid, Martina and Fehrmann, Rudolf Sn and Montgomery, Grant W and Hofman, Albert and Kao, Wen Hong Linda and Oostra, Ben A and Wright, Alan F and Vink, Jacqueline M and Wilson, James F and Pramstaller, Peter P and Hicks, Andrew A and Polasek, Ozren and Punjabi, Naresh M and Redline, Susan and Psaty, Bruce M and Heath, Andrew C and Merrow, Martha and Tranah, Gregory J and Gottlieb, Daniel J and Boomsma, Dorret I and Martin, Nicholas G and Rudan, Igor and Tiemeier, Henning and van IJcken, Wilfred Fj and Penninx, Brenda W and Metspalu, Andres and Meitinger, Thomas and Franke, Lude and Roenneberg, Till and van Duijn, Cornelia M} } @article {7594, title = {Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.}, journal = {JAMA Oncol}, volume = {3}, year = {2017}, month = {2017 May 01}, pages = {636-651}, abstract = {

Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.

Objective: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.

Data Sources: Genomewide association studies (GWAS) published up to January 15, 2015.

Study Selection: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.

Data Extraction and Synthesis: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.

Main Outcomes and Measures: Odds ratios (ORs) and 95\% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.

Results: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95\% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95\% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95\% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95\% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95\% CI, 0.05-0.15]).

Conclusions and Relevance: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

}, keywords = {Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Germ-Line Mutation, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Neoplasms, Polymorphism, Single Nucleotide, Risk Assessment, Telomere, Telomere Homeostasis}, issn = {2374-2445}, doi = {10.1001/jamaoncol.2016.5945}, author = {Haycock, Philip C and Burgess, Stephen and Nounu, Aayah and Zheng, Jie and Okoli, George N and Bowden, Jack and Wade, Kaitlin Hazel and Timpson, Nicholas J and Evans, David M and Willeit, Peter and Aviv, Abraham and Gaunt, Tom R and Hemani, Gibran and Mangino, Massimo and Ellis, Hayley Patricia and Kurian, Kathreena M and Pooley, Karen A and Eeles, Rosalind A and Lee, Jeffrey E and Fang, Shenying and Chen, Wei V and Law, Matthew H and Bowdler, Lisa M and Iles, Mark M and Yang, Qiong and Worrall, Bradford B and Markus, Hugh Stephen and Hung, Rayjean J and Amos, Chris I and Spurdle, Amanda B and Thompson, Deborah J and O{\textquoteright}Mara, Tracy A and Wolpin, Brian and Amundadottir, Laufey and Stolzenberg-Solomon, Rachael and Trichopoulou, Antonia and Onland-Moret, N Charlotte and Lund, Eiliv and Duell, Eric J and Canzian, Federico and Severi, Gianluca and Overvad, Kim and Gunter, Marc J and Tumino, Rosario and Svenson, Ulrika and van Rij, Andre and Baas, Annette F and Bown, Matthew J and Samani, Nilesh J and van t{\textquoteright}Hof, Femke N G and Tromp, Gerard and Jones, Gregory T and Kuivaniemi, Helena and Elmore, James R and Johansson, Mattias and Mckay, James and Scelo, Ghislaine and Carreras-Torres, Robert and Gaborieau, Valerie and Brennan, Paul and Bracci, Paige M and Neale, Rachel E and Olson, Sara H and Gallinger, Steven and Li, Donghui and Petersen, Gloria M and Risch, Harvey A and Klein, Alison P and Han, Jiali and Abnet, Christian C and Freedman, Neal D and Taylor, Philip R and Maris, John M and Aben, Katja K and Kiemeney, Lambertus A and Vermeulen, Sita H and Wiencke, John K and Walsh, Kyle M and Wrensch, Margaret and Rice, Terri and Turnbull, Clare and Litchfield, Kevin and Paternoster, Lavinia and Standl, Marie and Abecasis, Goncalo R and SanGiovanni, John Paul and Li, Yong and Mijatovic, Vladan and Sapkota, Yadav and Low, Siew-Kee and Zondervan, Krina T and Montgomery, Grant W and Nyholt, Dale R and van Heel, David A and Hunt, Karen and Arking, Dan E and Ashar, Foram N and Sotoodehnia, Nona and Woo, Daniel and Rosand, Jonathan and Comeau, Mary E and Brown, W Mark and Silverman, Edwin K and Hokanson, John E and Cho, Michael H and Hui, Jennie and Ferreira, Manuel A and Thompson, Philip J and Morrison, Alanna C and Felix, Janine F and Smith, Nicholas L and Christiano, Angela M and Petukhova, Lynn and Betz, Regina C and Fan, Xing and Zhang, Xuejun and Zhu, Caihong and Langefeld, Carl D and Thompson, Susan D and Wang, Feijie and Lin, Xu and Schwartz, David A and Fingerlin, Tasha and Rotter, Jerome I and Cotch, Mary Frances and Jensen, Richard A and Munz, Matthias and Dommisch, Henrik and Schaefer, Arne S and Han, Fang and Ollila, Hanna M and Hillary, Ryan P and Albagha, Omar and Ralston, Stuart H and Zeng, Chenjie and Zheng, Wei and Shu, Xiao-Ou and Reis, Andre and Uebe, Steffen and H{\"u}ffmeier, Ulrike and Kawamura, Yoshiya and Otowa, Takeshi and Sasaki, Tsukasa and Hibberd, Martin Lloyd and Davila, Sonia and Xie, Gang and Siminovitch, Katherine and Bei, Jin-Xin and Zeng, Yi-Xin and F{\"o}rsti, Asta and Chen, Bowang and Landi, Stefano and Franke, Andre and Fischer, Annegret and Ellinghaus, David and Flores, Carlos and Noth, Imre and Ma, Shwu-Fan and Foo, Jia Nee and Liu, Jianjun and Kim, Jong-Won and Cox, David G and Delattre, Olivier and Mirabeau, Olivier and Skibola, Christine F and Tang, Clara S and Garcia-Barcelo, Merce and Chang, Kai-Ping and Su, Wen-Hui and Chang, Yu-Sun and Martin, Nicholas G and Gordon, Scott and Wade, Tracey D and Lee, Chaeyoung and Kubo, Michiaki and Cha, Pei-Chieng and Nakamura, Yusuke and Levy, Daniel and Kimura, Masayuki and Hwang, Shih-Jen and Hunt, Steven and Spector, Tim and Soranzo, Nicole and Manichaikul, Ani W and Barr, R Graham and Kahali, Bratati and Speliotes, Elizabeth and Yerges-Armstrong, Laura M and Cheng, Ching-Yu and Jonas, Jost B and Wong, Tien Yin and Fogh, Isabella and Lin, Kuang and Powell, John F and Rice, Kenneth and Relton, Caroline L and Martin, Richard M and Davey Smith, George} } @article {7568, title = {Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.}, journal = {Nat Commun}, volume = {8}, year = {2017}, month = {2017 Oct 13}, pages = {910}, abstract = {

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents{\textquoteright} survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

}, issn = {2041-1723}, doi = {10.1038/s41467-017-00934-5}, author = {Joshi, Peter K and Pirastu, Nicola and Kentistou, Katherine A and Fischer, Krista and Hofer, Edith and Schraut, Katharina E and Clark, David W and Nutile, Teresa and Barnes, Catriona L K and Timmers, Paul R H J and Shen, Xia and Gandin, Ilaria and McDaid, Aaron F and Hansen, Thomas Folkmann and Gordon, Scott D and Giulianini, Franco and Boutin, Thibaud S and Abdellaoui, Abdel and Zhao, Wei and Medina-G{\'o}mez, Carolina and Bartz, Traci M and Trompet, Stella and Lange, Leslie A and Raffield, Laura and van der Spek, Ashley and Galesloot, Tessel E and Proitsi, Petroula and Yanek, Lisa R and Bielak, Lawrence F and Payton, Antony and Murgia, Federico and Concas, Maria Pina and Biino, Ginevra and Tajuddin, Salman M and Sepp{\"a}l{\"a}, Ilkka and Amin, Najaf and Boerwinkle, Eric and B{\o}rglum, Anders D and Campbell, Archie and Demerath, Ellen W and Demuth, Ilja and Faul, Jessica D and Ford, Ian and Gialluisi, Alessandro and G{\"o}gele, Martin and Graff, Mariaelisa and Hingorani, Aroon and Hottenga, Jouke-Jan and Hougaard, David M and Hurme, Mikko A and Ikram, M Arfan and Jylh{\"a}, Marja and Kuh, Diana and Ligthart, Lannie and Lill, Christina M and Lindenberger, Ulman and Lumley, Thomas and M{\"a}gi, Reedik and Marques-Vidal, Pedro and Medland, Sarah E and Milani, Lili and Nagy, Reka and Ollier, William E R and Peyser, Patricia A and Pramstaller, Peter P and Ridker, Paul M and Rivadeneira, Fernando and Ruggiero, Daniela and Saba, Yasaman and Schmidt, Reinhold and Schmidt, Helena and Slagboom, P Eline and Smith, Blair H and Smith, Jennifer A and Sotoodehnia, Nona and Steinhagen-Thiessen, Elisabeth and van Rooij, Frank J A and Verbeek, Andr{\'e} L and Vermeulen, Sita H and Vollenweider, Peter and Wang, Yunpeng and Werge, Thomas and Whitfield, John B and Zonderman, Alan B and Lehtim{\"a}ki, Terho and Evans, Michele K and Pirastu, Mario and Fuchsberger, Christian and Bertram, Lars and Pendleton, Neil and Kardia, Sharon L R and Ciullo, Marina and Becker, Diane M and Wong, Andrew and Psaty, Bruce M and van Duijn, Cornelia M and Wilson, James G and Jukema, J Wouter and Kiemeney, Lambertus and Uitterlinden, Andr{\'e} G and Franceschini, Nora and North, Kari E and Weir, David R and Metspalu, Andres and Boomsma, Dorret I and Hayward, Caroline and Chasman, Daniel and Martin, Nicholas G and Sattar, Naveed and Campbell, Harry and Esko, T{\~o}nu and Kutalik, Zolt{\'a}n and Wilson, James F} } @article {7920, title = {Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders.}, journal = {Am J Hum Genet}, volume = {103}, year = {2018}, month = {2018 Nov 01}, pages = {691-706}, abstract = {

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5~{\texttimes} 10). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0\% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2018.09.009}, author = {Ligthart, Symen and Vaez, Ahmad and V{\~o}sa, Urmo and Stathopoulou, Maria G and de Vries, Paul S and Prins, Bram P and van der Most, Peter J and Tanaka, Toshiko and Naderi, Elnaz and Rose, Lynda M and Wu, Ying and Karlsson, Robert and Barbalic, Maja and Lin, Honghuang and Pool, Rene and Zhu, Gu and Mace, Aurelien and Sidore, Carlo and Trompet, Stella and Mangino, Massimo and Sabater-Lleal, Maria and Kemp, John P and Abbasi, Ali and Kacprowski, Tim and Verweij, Niek and Smith, Albert V and Huang, Tao and Marzi, Carola and Feitosa, Mary F and Lohman, Kurt K and Kleber, Marcus E and Milaneschi, Yuri and Mueller, Christian and Huq, Mahmudul and Vlachopoulou, Efthymia and Lyytik{\"a}inen, Leo-Pekka and Oldmeadow, Christopher and Deelen, Joris and Perola, Markus and Zhao, Jing Hua and Feenstra, Bjarke and Amini, Marzyeh and Lahti, Jari and Schraut, Katharina E and Fornage, Myriam and Suktitipat, Bhoom and Chen, Wei-Min and Li, Xiaohui and Nutile, Teresa and Malerba, Giovanni and Luan, Jian{\textquoteright}an and Bak, Tom and Schork, Nicholas and del Greco M, Fabiola and Thiering, Elisabeth and Mahajan, Anubha and Marioni, Riccardo E and Mihailov, Evelin and Eriksson, Joel and Ozel, Ayse Bilge and Zhang, Weihua and Nethander, Maria and Cheng, Yu-Ching and Aslibekyan, Stella and Ang, Wei and Gandin, Ilaria and Yengo, Loic and Portas, Laura and Kooperberg, Charles and Hofer, Edith and Rajan, Kumar B and Schurmann, Claudia and den Hollander, Wouter and Ahluwalia, Tarunveer S and Zhao, Jing and Draisma, Harmen H M and Ford, Ian and Timpson, Nicholas and Teumer, Alexander and Huang, Hongyan and Wahl, Simone and Liu, Yongmei and Huang, Jie and Uh, Hae-Won and Geller, Frank and Joshi, Peter K and Yanek, Lisa R and Trabetti, Elisabetta and Lehne, Benjamin and Vozzi, Diego and Verbanck, Marie and Biino, Ginevra and Saba, Yasaman and Meulenbelt, Ingrid and O{\textquoteright}Connell, Jeff R and Laakso, Markku and Giulianini, Franco and Magnusson, Patrik K E and Ballantyne, Christie M and Hottenga, Jouke Jan and Montgomery, Grant W and Rivadineira, Fernando and Rueedi, Rico and Steri, Maristella and Herzig, Karl-Heinz and Stott, David J and Menni, Cristina and Fr{\r a}nberg, Mattias and St Pourcain, Beate and Felix, Stephan B and Pers, Tune H and Bakker, Stephan J L and Kraft, Peter and Peters, Annette and Vaidya, Dhananjay and Delgado, Graciela and Smit, Johannes H and Gro{\ss}mann, Vera and Sinisalo, Juha and Sepp{\"a}l{\"a}, Ilkka and Williams, Stephen R and Holliday, Elizabeth G and Moed, Matthijs and Langenberg, Claudia and R{\"a}ikk{\"o}nen, Katri and Ding, Jingzhong and Campbell, Harry and Sale, Mich{\`e}le M and Chen, Yii-der I and James, Alan L and Ruggiero, Daniela and Soranzo, Nicole and Hartman, Catharina A and Smith, Erin N and Berenson, Gerald S and Fuchsberger, Christian and Hernandez, Dena and Tiesler, Carla M T and Giedraitis, Vilmantas and Liewald, David and Fischer, Krista and Mellstr{\"o}m, Dan and Larsson, Anders and Wang, Yunmei and Scott, William R and Lorentzon, Matthias and Beilby, John and Ryan, Kathleen A and Pennell, Craig E and Vuckovic, Dragana and Balkau, Beverly and Concas, Maria Pina and Schmidt, Reinhold and Mendes de Leon, Carlos F and Bottinger, Erwin P and Kloppenburg, Margreet and Paternoster, Lavinia and Boehnke, Michael and Musk, A W and Willemsen, Gonneke and Evans, David M and Madden, Pamela A F and K{\"a}h{\"o}nen, Mika and Kutalik, Zolt{\'a}n and Zoledziewska, Magdalena and Karhunen, Ville and Kritchevsky, Stephen B and Sattar, Naveed and Lachance, Genevieve and Clarke, Robert and Harris, Tamara B and Raitakari, Olli T and Attia, John R and van Heemst, Diana and Kajantie, Eero and Sorice, Rossella and Gambaro, Giovanni and Scott, Robert A and Hicks, Andrew A and Ferrucci, Luigi and Standl, Marie and Lindgren, Cecilia M and Starr, John M and Karlsson, Magnus and Lind, Lars and Li, Jun Z and Chambers, John C and Mori, Trevor A and de Geus, Eco J C N and Heath, Andrew C and Martin, Nicholas G and Auvinen, Juha and Buckley, Brendan M and de Craen, Anton J M and Waldenberger, Melanie and Strauch, Konstantin and Meitinger, Thomas and Scott, Rodney J and McEvoy, Mark and Beekman, Marian and Bombieri, Cristina and Ridker, Paul M and Mohlke, Karen L and Pedersen, Nancy L and Morrison, Alanna C and Boomsma, Dorret I and Whitfield, John B and Strachan, David P and Hofman, Albert and Vollenweider, Peter and Cucca, Francesco and Jarvelin, Marjo-Riitta and Jukema, J Wouter and Spector, Tim D and Hamsten, Anders and Zeller, Tanja and Uitterlinden, Andr{\'e} G and Nauck, Matthias and Gudnason, Vilmundur and Qi, Lu and Grallert, Harald and Borecki, Ingrid B and Rotter, Jerome I and M{\"a}rz, Winfried and Wild, Philipp S and Lokki, Marja-Liisa and Boyle, Michael and Salomaa, Veikko and Melbye, Mads and Eriksson, Johan G and Wilson, James F and Penninx, Brenda W J H and Becker, Diane M and Worrall, Bradford B and Gibson, Greg and Krauss, Ronald M and Ciullo, Marina and Zaza, Gianluigi and Wareham, Nicholas J and Oldehinkel, Albertine J and Palmer, Lyle J and Murray, Sarah S and Pramstaller, Peter P and Bandinelli, Stefania and Heinrich, Joachim and Ingelsson, Erik and Deary, Ian J and M{\"a}gi, Reedik and Vandenput, Liesbeth and van der Harst, Pim and Desch, Karl C and Kooner, Jaspal S and Ohlsson, Claes and Hayward, Caroline and Lehtim{\"a}ki, Terho and Shuldiner, Alan R and Arnett, Donna K and Beilin, Lawrence J and Robino, Antonietta and Froguel, Philippe and Pirastu, Mario and Jess, Tine and Koenig, Wolfgang and Loos, Ruth J F and Evans, Denis A and Schmidt, Helena and Smith, George Davey and Slagboom, P Eline and Eiriksdottir, Gudny and Morris, Andrew P and Psaty, Bruce M and Tracy, Russell P and Nolte, Ilja M and Boerwinkle, Eric and Visvikis-Siest, Sophie and Reiner, Alex P and Gross, Myron and Bis, Joshua C and Franke, Lude and Franco, Oscar H and Benjamin, Emelia J and Chasman, Daniel I and Dupuis, Jos{\'e}e and Snieder, Harold and Dehghan, Abbas and Alizadeh, Behrooz Z} } @article {7788, title = {Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.}, journal = {Nat Commun}, volume = {9}, year = {2018}, month = {2018 May 29}, pages = {2098}, abstract = {

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 {\texttimes} 10) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3\% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

}, issn = {2041-1723}, doi = {10.1038/s41467-018-04362-x}, author = {Davies, Gail and Lam, Max and Harris, Sarah E and Trampush, Joey W and Luciano, Michelle and Hill, W David and Hagenaars, Saskia P and Ritchie, Stuart J and Marioni, Riccardo E and Fawns-Ritchie, Chloe and Liewald, David C M and Okely, Judith A and Ahola-Olli, Ari V and Barnes, Catriona L K and Bertram, Lars and Bis, Joshua C and Burdick, Katherine E and Christoforou, Andrea and DeRosse, Pamela and Djurovic, Srdjan and Espeseth, Thomas and Giakoumaki, Stella and Giddaluru, Sudheer and Gustavson, Daniel E and Hayward, Caroline and Hofer, Edith and Ikram, M Arfan and Karlsson, Robert and Knowles, Emma and Lahti, Jari and Leber, Markus and Li, Shuo and Mather, Karen A and Melle, Ingrid and Morris, Derek and Oldmeadow, Christopher and Palviainen, Teemu and Payton, Antony and Pazoki, Raha and Petrovic, Katja and Reynolds, Chandra A and Sargurupremraj, Muralidharan and Scholz, Markus and Smith, Jennifer A and Smith, Albert V and Terzikhan, Natalie and Thalamuthu, Anbupalam and Trompet, Stella and van der Lee, Sven J and Ware, Erin B and Windham, B Gwen and Wright, Margaret J and Yang, Jingyun and Yu, Jin and Ames, David and Amin, Najaf and Amouyel, Philippe and Andreassen, Ole A and Armstrong, Nicola J and Assareh, Amelia A and Attia, John R and Attix, Deborah and Avramopoulos, Dimitrios and Bennett, David A and B{\"o}hmer, Anne C and Boyle, Patricia A and Brodaty, Henry and Campbell, Harry and Cannon, Tyrone D and Cirulli, Elizabeth T and Congdon, Eliza and Conley, Emily Drabant and Corley, Janie and Cox, Simon R and Dale, Anders M and Dehghan, Abbas and Dick, Danielle and Dickinson, Dwight and Eriksson, Johan G and Evangelou, Evangelos and Faul, Jessica D and Ford, Ian and Freimer, Nelson A and Gao, He and Giegling, Ina and Gillespie, Nathan A and Gordon, Scott D and Gottesman, Rebecca F and Griswold, Michael E and Gudnason, Vilmundur and Harris, Tamara B and Hartmann, Annette M and Hatzimanolis, Alex and Heiss, Gerardo and Holliday, Elizabeth G and Joshi, Peter K and K{\"a}h{\"o}nen, Mika and Kardia, Sharon L R and Karlsson, Ida and Kleineidam, Luca and Knopman, David S and Kochan, Nicole A and Konte, Bettina and Kwok, John B and Le Hellard, Stephanie and Lee, Teresa and Lehtim{\"a}ki, Terho and Li, Shu-Chen and Liu, Tian and Koini, Marisa and London, Edythe and Longstreth, Will T and Lopez, Oscar L and Loukola, Anu and Luck, Tobias and Lundervold, Astri J and Lundquist, Anders and Lyytik{\"a}inen, Leo-Pekka and Martin, Nicholas G and Montgomery, Grant W and Murray, Alison D and Need, Anna C and Noordam, Raymond and Nyberg, Lars and Ollier, William and Papenberg, Goran and Pattie, Alison and Polasek, Ozren and Poldrack, Russell A and Psaty, Bruce M and Reppermund, Simone and Riedel-Heller, Steffi G and Rose, Richard J and Rotter, Jerome I and Roussos, Panos and Rovio, Suvi P and Saba, Yasaman and Sabb, Fred W and Sachdev, Perminder S and Satizabal, Claudia L and Schmid, Matthias and Scott, Rodney J and Scult, Matthew A and Simino, Jeannette and Slagboom, P Eline and Smyrnis, Nikolaos and Soumar{\'e}, A{\"\i}cha and Stefanis, Nikos C and Stott, David J and Straub, Richard E and Sundet, Kjetil and Taylor, Adele M and Taylor, Kent D and Tzoulaki, Ioanna and Tzourio, Christophe and Uitterlinden, Andre and Vitart, Veronique and Voineskos, Aristotle N and Kaprio, Jaakko and Wagner, Michael and Wagner, Holger and Weinhold, Leonie and Wen, K Hoyan and Widen, Elisabeth and Yang, Qiong and Zhao, Wei and Adams, Hieab H H and Arking, Dan E and Bilder, Robert M and Bitsios, Panos and Boerwinkle, Eric and Chiba-Falek, Ornit and Corvin, Aiden and De Jager, Philip L and Debette, Stephanie and Donohoe, Gary and Elliott, Paul and Fitzpatrick, Annette L and Gill, Michael and Glahn, David C and H{\"a}gg, Sara and Hansell, Narelle K and Hariri, Ahmad R and Ikram, M Kamran and Jukema, J Wouter and Vuoksimaa, Eero and Keller, Matthew C and Kremen, William S and Launer, Lenore and Lindenberger, Ulman and Palotie, Aarno and Pedersen, Nancy L and Pendleton, Neil and Porteous, David J and R{\"a}ikk{\"o}nen, Katri and Raitakari, Olli T and Ramirez, Alfredo and Reinvang, Ivar and Rudan, Igor and Schmidt, Reinhold and Schmidt, Helena and Schofield, Peter W and Schofield, Peter R and Starr, John M and Steen, Vidar M and Trollor, Julian N and Turner, Steven T and van Duijn, Cornelia M and Villringer, Arno and Weinberger, Daniel R and Weir, David R and Wilson, James F and Malhotra, Anil and McIntosh, Andrew M and Gale, Catharine R and Seshadri, Sudha and Mosley, Thomas H and Bressler, Jan and Lencz, Todd and Deary, Ian J} } @article {8198, title = {Associations of autozygosity with a broad range of human phenotypes.}, journal = {Nat Commun}, volume = {10}, year = {2019}, month = {2019 Oct 31}, pages = {4957}, abstract = {

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.4 million individuals, we show that F is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F equivalent to the offspring of first cousins is associated with a 55\% decrease [95\% CI 44-66\%] in the odds of having children. Finally, the effects of F are confirmed within full-sibling pairs, where the variation in F is independent of all environmental confounding.

}, issn = {2041-1723}, doi = {10.1038/s41467-019-12283-6}, author = {Clark, David W and Okada, Yukinori and Moore, Kristjan H S and Mason, Dan and Pirastu, Nicola and Gandin, Ilaria and Mattsson, Hannele and Barnes, Catriona L K and Lin, Kuang and Zhao, Jing Hua and Deelen, Patrick and Rohde, Rebecca and Schurmann, Claudia and Guo, Xiuqing and Giulianini, Franco and Zhang, Weihua and Medina-G{\'o}mez, Carolina and Karlsson, Robert and Bao, Yanchun and Bartz, Traci M and Baumbach, Clemens and Biino, Ginevra and Bixley, Matthew J and Brumat, Marco and Chai, Jin-Fang and Corre, Tanguy and Cousminer, Diana L and Dekker, Annelot M and Eccles, David A and van Eijk, Kristel R and Fuchsberger, Christian and Gao, He and Germain, Marine and Gordon, Scott D and de Haan, Hugoline G and Harris, Sarah E and Hofer, Edith and Huerta-Chagoya, Alicia and Igartua, Catherine and Jansen, Iris E and Jia, Yucheng and Kacprowski, Tim and Karlsson, Torgny and Kleber, Marcus E and Li, Shengchao Alfred and Li-Gao, Ruifang and Mahajan, Anubha and Matsuda, Koichi and Meidtner, Karina and Meng, Weihua and Montasser, May E and van der Most, Peter J and Munz, Matthias and Nutile, Teresa and Palviainen, Teemu and Prasad, Gauri and Prasad, Rashmi B and Priyanka, Tallapragada Divya Sri and Rizzi, Federica and Salvi, Erika and Sapkota, Bishwa R and Shriner, Daniel and Skotte, Line and Smart, Melissa C and Smith, Albert Vernon and van der Spek, Ashley and Spracklen, Cassandra N and Strawbridge, Rona J and Tajuddin, Salman M and Trompet, Stella and Turman, Constance and Verweij, Niek and Viberti, Clara and Wang, Lihua and Warren, Helen R and Wootton, Robyn E and Yanek, Lisa R and Yao, Jie and Yousri, Noha A and Zhao, Wei and Adeyemo, Adebowale A and Afaq, Saima and Aguilar-Salinas, Carlos Alberto and Akiyama, Masato and Albert, Matthew L and Allison, Matthew A and Alver, Maris and Aung, Tin and Azizi, Fereidoun and Bentley, Amy R and Boeing, Heiner and Boerwinkle, Eric and Borja, Judith B and de Borst, Gert J and Bottinger, Erwin P and Broer, Linda and Campbell, Harry and Chanock, Stephen and Chee, Miao-Li and Chen, Guanjie and Chen, Yii-der I and Chen, Zhengming and Chiu, Yen-Feng and Cocca, Massimiliano and Collins, Francis S and Concas, Maria Pina and Corley, Janie and Cugliari, Giovanni and van Dam, Rob M and Damulina, Anna and Daneshpour, Maryam S and Day, Felix R and Delgado, Graciela E and Dhana, Klodian and Doney, Alexander S F and D{\"o}rr, Marcus and Doumatey, Ayo P and Dzimiri, Nduna and Ebenesersd{\'o}ttir, S Sunna and Elliott, Joshua and Elliott, Paul and Ewert, Ralf and Felix, Janine F and Fischer, Krista and Freedman, Barry I and Girotto, Giorgia and Goel, Anuj and G{\"o}gele, Martin and Goodarzi, Mark O and Graff, Mariaelisa and Granot-Hershkovitz, Einat and Grodstein, Francine and Guarrera, Simonetta and Gudbjartsson, Daniel F and Guity, Kamran and Gunnarsson, Bjarni and Guo, Yu and Hagenaars, Saskia P and Haiman, Christopher A and Halevy, Avner and Harris, Tamara B and Hedayati, Mehdi and van Heel, David A and Hirata, Makoto and H{\"o}fer, Imo and Hsiung, Chao Agnes and Huang, Jinyan and Hung, Yi-Jen and Ikram, M Arfan and Jagadeesan, Anuradha and Jousilahti, Pekka and Kamatani, Yoichiro and Kanai, Masahiro and Kerrison, Nicola D and Kessler, Thorsten and Khaw, Kay-Tee and Khor, Chiea Chuen and de Kleijn, Dominique P V and Koh, Woon-Puay and Kolcic, Ivana and Kraft, Peter and Kr{\"a}mer, Bernhard K and Kutalik, Zolt{\'a}n and Kuusisto, Johanna and Langenberg, Claudia and Launer, Lenore J and Lawlor, Deborah A and Lee, I-Te and Lee, Wen-Jane and Lerch, Markus M and Li, Liming and Liu, Jianjun and Loh, Marie and London, Stephanie J and Loomis, Stephanie and Lu, Yingchang and Luan, Jian{\textquoteright}an and M{\"a}gi, Reedik and Manichaikul, Ani W and Manunta, Paolo and M{\'a}sson, G{\'\i}sli and Matoba, Nana and Mei, Xue W and Meisinger, Christa and Meitinger, Thomas and Mezzavilla, Massimo and Milani, Lili and Millwood, Iona Y and Momozawa, Yukihide and Moore, Amy and Morange, Pierre-Emmanuel and Moreno-Macias, Hortensia and Mori, Trevor A and Morrison, Alanna C and Muka, Taulant and Murakami, Yoshinori and Murray, Alison D and de Mutsert, Ren{\'e}e and Mychaleckyj, Josyf C and Nalls, Mike A and Nauck, Matthias and Neville, Matt J and Nolte, Ilja M and Ong, Ken K and Orozco, Lorena and Padmanabhan, Sandosh and P{\'a}lsson, Gunnar and Pankow, James S and Pattaro, Cristian and Pattie, Alison and Polasek, Ozren and Poulter, Neil and Pramstaller, Peter P and Quintana-Murci, Lluis and R{\"a}ikk{\"o}nen, Katri and Ralhan, Sarju and Rao, Dabeeru C and van Rheenen, Wouter and Rich, Stephen S and Ridker, Paul M and Rietveld, Cornelius A and Robino, Antonietta and van Rooij, Frank J A and Ruggiero, Daniela and Saba, Yasaman and Sabanayagam, Charumathi and Sabater-Lleal, Maria and Sala, Cinzia Felicita and Salomaa, Veikko and Sandow, Kevin and Schmidt, Helena and Scott, Laura J and Scott, William R and Sedaghati-Khayat, Bahareh and Sennblad, Bengt and van Setten, Jessica and Sever, Peter J and Sheu, Wayne H-H and Shi, Yuan and Shrestha, Smeeta and Shukla, Sharvari Rahul and Sigurdsson, Jon K and Sikka, Timo Tonis and Singh, Jai Rup and Smith, Blair H and Stan{\v c}{\'a}kov{\'a}, Alena and Stanton, Alice and Starr, John M and Stefansdottir, Lilja and Straker, Leon and Sulem, Patrick and Sveinbjornsson, Gardar and Swertz, Morris A and Taylor, Adele M and Taylor, Kent D and Terzikhan, Natalie and Tham, Yih-Chung and Thorleifsson, Gudmar and Thorsteinsdottir, Unnur and Tillander, Annika and Tracy, Russell P and Tusi{\'e}-Luna, Teresa and Tzoulaki, Ioanna and Vaccargiu, Simona and Vangipurapu, Jagadish and Veldink, Jan H and Vitart, Veronique and V{\"o}lker, Uwe and Vuoksimaa, Eero and Wakil, Salma M and Waldenberger, Melanie and Wander, Gurpreet S and Wang, Ya Xing and Wareham, Nicholas J and Wild, Sarah and Yajnik, Chittaranjan S and Yuan, Jian-Min and Zeng, Lingyao and Zhang, Liang and Zhou, Jie and Amin, Najaf and Asselbergs, Folkert W and Bakker, Stephan J L and Becker, Diane M and Lehne, Benjamin and Bennett, David A and van den Berg, Leonard H and Berndt, Sonja I and Bharadwaj, Dwaipayan and Bielak, Lawrence F and Bochud, Murielle and Boehnke, Mike and Bouchard, Claude and Bradfield, Jonathan P and Brody, Jennifer A and Campbell, Archie and Carmi, Shai and Caulfield, Mark J and Cesarini, David and Chambers, John C and Chandak, Giriraj Ratan and Cheng, Ching-Yu and Ciullo, Marina and Cornelis, Marilyn and Cusi, Daniele and Smith, George Davey and Deary, Ian J and Dorajoo, Rajkumar and van Duijn, Cornelia M and Ellinghaus, David and Erdmann, Jeanette and Eriksson, Johan G and Evangelou, Evangelos and Evans, Michele K and Faul, Jessica D and Feenstra, Bjarke and Feitosa, Mary and Foisy, Sylvain and Franke, Andre and Friedlander, Yechiel and Gasparini, Paolo and Gieger, Christian and Gonzalez, Clicerio and Goyette, Philippe and Grant, Struan F A and Griffiths, Lyn R and Groop, Leif and Gudnason, Vilmundur and Gyllensten, Ulf and Hakonarson, Hakon and Hamsten, Anders and van der Harst, Pim and Heng, Chew-Kiat and Hicks, Andrew A and Hochner, Hagit and Huikuri, Heikki and Hunt, Steven C and Jaddoe, Vincent W V and De Jager, Philip L and Johannesson, Magnus and Johansson, Asa and Jonas, Jost B and Jukema, J Wouter and Junttila, Juhani and Kaprio, Jaakko and Kardia, Sharon L R and Karpe, Fredrik and Kumari, Meena and Laakso, Markku and van der Laan, Sander W and Lahti, Jari and Laudes, Matthias and Lea, Rodney A and Lieb, Wolfgang and Lumley, Thomas and Martin, Nicholas G and M{\"a}rz, Winfried and Matullo, Giuseppe and McCarthy, Mark I and Medland, Sarah E and Merriman, Tony R and Metspalu, Andres and Meyer, Brian F and Mohlke, Karen L and Montgomery, Grant W and Mook-Kanamori, Dennis and Munroe, Patricia B and North, Kari E and Nyholt, Dale R and O{\textquoteright}Connell, Jeffery R and Ober, Carole and Oldehinkel, Albertine J and Palmas, Walter and Palmer, Colin and Pasterkamp, Gerard G and Patin, Etienne and Pennell, Craig E and Perusse, Louis and Peyser, Patricia A and Pirastu, Mario and Polderman, Tinca J C and Porteous, David J and Posthuma, Danielle and Psaty, Bruce M and Rioux, John D and Rivadeneira, Fernando and Rotimi, Charles and Rotter, Jerome I and Rudan, Igor and den Ruijter, Hester M and Sanghera, Dharambir K and Sattar, Naveed and Schmidt, Reinhold and Schulze, Matthias B and Schunkert, Heribert and Scott, Robert A and Shuldiner, Alan R and Sim, Xueling and Small, Neil and Smith, Jennifer A and Sotoodehnia, Nona and Tai, E-Shyong and Teumer, Alexander and Timpson, Nicholas J and Toniolo, Daniela and Tr{\'e}gou{\"e}t, David-Alexandre and Tuomi, Tiinamaija and Vollenweider, Peter and Wang, Carol A and Weir, David R and Whitfield, John B and Wijmenga, Cisca and Wong, Tien-Yin and Wright, John and Yang, Jingyun and Yu, Lei and Zemel, Babette S and Zonderman, Alan B and Perola, Markus and Magnusson, Patrik K E and Uitterlinden, Andr{\'e} G and Kooner, Jaspal S and Chasman, Daniel I and Loos, Ruth J F and Franceschini, Nora and Franke, Lude and Haley, Chris S and Hayward, Caroline and Walters, Robin G and Perry, John R B and Esko, T{\~o}nu and Helgason, Agnar and Stefansson, Kari and Joshi, Peter K and Kubo, Michiaki and Wilson, James F} } @article {8109, title = {A catalog of genetic loci associated with kidney function from analyses of a million individuals.}, journal = {Nat Genet}, volume = {51}, year = {2019}, month = {2019 06}, pages = {957-972}, abstract = {

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

}, keywords = {Chromosome Mapping, European Continental Ancestry Group, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Inheritance Patterns, Kidney Function Tests, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Renal Insufficiency, Chronic, Uromodulin}, issn = {1546-1718}, doi = {10.1038/s41588-019-0407-x}, author = {Wuttke, Matthias and Li, Yong and Li, Man and Sieber, Karsten B and Feitosa, Mary F and Gorski, Mathias and Tin, Adrienne and Wang, Lihua and Chu, Audrey Y and Hoppmann, Anselm and Kirsten, Holger and Giri, Ayush and Chai, Jin-Fang and Sveinbjornsson, Gardar and Tayo, Bamidele O and Nutile, Teresa and Fuchsberger, Christian and Marten, Jonathan and Cocca, Massimiliano and Ghasemi, Sahar and Xu, Yizhe and Horn, Katrin and Noce, Damia and van der Most, Peter J and Sedaghat, Sanaz and Yu, Zhi and Akiyama, Masato and Afaq, Saima and Ahluwalia, Tarunveer S and Almgren, Peter and Amin, Najaf and Arnl{\"o}v, Johan and Bakker, Stephan J L and Bansal, Nisha and Baptista, Daniela and Bergmann, Sven and Biggs, Mary L and Biino, Ginevra and Boehnke, Michael and Boerwinkle, Eric and Boissel, Mathilde and Bottinger, Erwin P and Boutin, Thibaud S and Brenner, Hermann and Brumat, Marco and Burkhardt, Ralph and Butterworth, Adam S and Campana, Eric and Campbell, Archie and Campbell, Harry and Canouil, Micka{\"e}l and Carroll, Robert J and Catamo, Eulalia and Chambers, John C and Chee, Miao-Ling and Chee, Miao-Li and Chen, Xu and Cheng, Ching-Yu and Cheng, Yurong and Christensen, Kaare and Cifkova, Renata and Ciullo, Marina and Concas, Maria Pina and Cook, James P and Coresh, Josef and Corre, Tanguy and Sala, Cinzia Felicita and Cusi, Daniele and Danesh, John and Daw, E Warwick and de Borst, Martin H and De Grandi, Alessandro and de Mutsert, Ren{\'e}e and de Vries, Aiko P J and Degenhardt, Frauke and Delgado, Graciela and Demirkan, Ayse and Di Angelantonio, Emanuele and Dittrich, Katalin and Divers, Jasmin and Dorajoo, Rajkumar and Eckardt, Kai-Uwe and Ehret, Georg and Elliott, Paul and Endlich, Karlhans and Evans, Michele K and Felix, Janine F and Foo, Valencia Hui Xian and Franco, Oscar H and Franke, Andre and Freedman, Barry I and Freitag-Wolf, Sandra and Friedlander, Yechiel and Froguel, Philippe and Gansevoort, Ron T and Gao, He and Gasparini, Paolo and Gaziano, J Michael and Giedraitis, Vilmantas and Gieger, Christian and Girotto, Giorgia and Giulianini, Franco and G{\"o}gele, Martin and Gordon, Scott D and Gudbjartsson, Daniel F and Gudnason, Vilmundur and Haller, Toomas and Hamet, Pavel and Harris, Tamara B and Hartman, Catharina A and Hayward, Caroline and Hellwege, Jacklyn N and Heng, Chew-Kiat and Hicks, Andrew A and Hofer, Edith and Huang, Wei and Hutri-K{\"a}h{\"o}nen, Nina and Hwang, Shih-Jen and Ikram, M Arfan and Indridason, Olafur S and Ingelsson, Erik and Ising, Marcus and Jaddoe, Vincent W V and Jakobsdottir, Johanna and Jonas, Jost B and Joshi, Peter K and Josyula, Navya Shilpa and Jung, Bettina and K{\"a}h{\"o}nen, Mika and Kamatani, Yoichiro and Kammerer, Candace M and Kanai, Masahiro and Kastarinen, Mika and Kerr, Shona M and Khor, Chiea-Chuen and Kiess, Wieland and Kleber, Marcus E and Koenig, Wolfgang and Kooner, Jaspal S and K{\"o}rner, Antje and Kovacs, Peter and Kraja, Aldi T and Krajcoviechova, Alena and Kramer, Holly and Kr{\"a}mer, Bernhard K and Kronenberg, Florian and Kubo, Michiaki and Kuhnel, Brigitte and Kuokkanen, Mikko and Kuusisto, Johanna and La Bianca, Martina and Laakso, Markku and Lange, Leslie A and Langefeld, Carl D and Lee, Jeannette Jen-Mai and Lehne, Benjamin and Lehtim{\"a}ki, Terho and Lieb, Wolfgang and Lim, Su-Chi and Lind, Lars and Lindgren, Cecilia M and Liu, Jun and Liu, Jianjun and Loeffler, Markus and Loos, Ruth J F and Lucae, Susanne and Lukas, Mary Ann and Lyytik{\"a}inen, Leo-Pekka and M{\"a}gi, Reedik and Magnusson, Patrik K E and Mahajan, Anubha and Martin, Nicholas G and Martins, Jade and M{\"a}rz, Winfried and Mascalzoni, Deborah and Matsuda, Koichi and Meisinger, Christa and Meitinger, Thomas and Melander, Olle and Metspalu, Andres and Mikaelsdottir, Evgenia K and Milaneschi, Yuri and Miliku, Kozeta and Mishra, Pashupati P and Mohlke, Karen L and Mononen, Nina and Montgomery, Grant W and Mook-Kanamori, Dennis O and Mychaleckyj, Josyf C and Nadkarni, Girish N and Nalls, Mike A and Nauck, Matthias and Nikus, Kjell and Ning, Boting and Nolte, Ilja M and Noordam, Raymond and O{\textquoteright}Connell, Jeffrey and O{\textquoteright}Donoghue, Michelle L and Olafsson, Isleifur and Oldehinkel, Albertine J and Orho-Melander, Marju and Ouwehand, Willem H and Padmanabhan, Sandosh and Palmer, Nicholette D and Palsson, Runolfur and Penninx, Brenda W J H and Perls, Thomas and Perola, Markus and Pirastu, Mario and Pirastu, Nicola and Pistis, Giorgio and Podgornaia, Anna I and Polasek, Ozren and Ponte, Belen and Porteous, David J and Poulain, Tanja and Pramstaller, Peter P and Preuss, Michael H and Prins, Bram P and Province, Michael A and Rabelink, Ton J and Raffield, Laura M and Raitakari, Olli T and Reilly, Dermot F and Rettig, Rainer and Rheinberger, Myriam and Rice, Kenneth M and Ridker, Paul M and Rivadeneira, Fernando and Rizzi, Federica and Roberts, David J and Robino, Antonietta and Rossing, Peter and Rudan, Igor and Rueedi, Rico and Ruggiero, Daniela and Ryan, Kathleen A and Saba, Yasaman and Sabanayagam, Charumathi and Salomaa, Veikko and Salvi, Erika and Saum, Kai-Uwe and Schmidt, Helena and Schmidt, Reinhold and Sch{\"o}ttker, Ben and Schulz, Christina-Alexandra and Schupf, Nicole and Shaffer, Christian M and Shi, Yuan and Smith, Albert V and Smith, Blair H and Soranzo, Nicole and Spracklen, Cassandra N and Strauch, Konstantin and Stringham, Heather M and Stumvoll, Michael and Svensson, Per O and Szymczak, Silke and Tai, E-Shyong and Tajuddin, Salman M and Tan, Nicholas Y Q and Taylor, Kent D and Teren, Andrej and Tham, Yih-Chung and Thiery, Joachim and Thio, Chris H L and Thomsen, Hauke and Thorleifsson, Gudmar and Toniolo, Daniela and T{\"o}njes, Anke and Tremblay, Johanne and Tzoulaki, Ioanna and Uitterlinden, Andr{\'e} G and Vaccargiu, Simona and van Dam, Rob M and van der Harst, Pim and van Duijn, Cornelia M and Velez Edward, Digna R and Verweij, Niek and Vogelezang, Suzanne and V{\"o}lker, Uwe and Vollenweider, Peter and Waeber, G{\'e}rard and Waldenberger, Melanie and Wallentin, Lars and Wang, Ya Xing and Wang, Chaolong and Waterworth, Dawn M and Bin Wei, Wen and White, Harvey and Whitfield, John B and Wild, Sarah H and Wilson, James F and Wojczynski, Mary K and Wong, Charlene and Wong, Tien-Yin and Xu, Liang and Yang, Qiong and Yasuda, Masayuki and Yerges-Armstrong, Laura M and Zhang, Weihua and Zonderman, Alan B and Rotter, Jerome I and Bochud, Murielle and Psaty, Bruce M and Vitart, Veronique and Wilson, James G and Dehghan, Abbas and Parsa, Afshin and Chasman, Daniel I and Ho, Kevin and Morris, Andrew P and Devuyst, Olivier and Akilesh, Shreeram and Pendergrass, Sarah A and Sim, Xueling and B{\"o}ger, Carsten A and Okada, Yukinori and Edwards, Todd L and Snieder, Harold and Stefansson, Kari and Hung, Adriana M and Heid, Iris M and Scholz, Markus and Teumer, Alexander and K{\"o}ttgen, Anna and Pattaro, Cristian} } @article {8206, title = {Genetic architecture of subcortical brain structures in 38,851 individuals.}, journal = {Nat Genet}, volume = {51}, year = {2019}, month = {2019 Nov}, pages = {1624-1636}, abstract = {

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

}, issn = {1546-1718}, doi = {10.1038/s41588-019-0511-y}, author = {Satizabal, Claudia L and Adams, Hieab H H and Hibar, Derrek P and White, Charles C and Knol, Maria J and Stein, Jason L and Scholz, Markus and Sargurupremraj, Muralidharan and Jahanshad, Neda and Roshchupkin, Gennady V and Smith, Albert V and Bis, Joshua C and Jian, Xueqiu and Luciano, Michelle and Hofer, Edith and Teumer, Alexander and van der Lee, Sven J and Yang, Jingyun and Yanek, Lisa R and Lee, Tom V and Li, Shuo and Hu, Yanhui and Koh, Jia Yu and Eicher, John D and Desrivi{\`e}res, Sylvane and Arias-Vasquez, Alejandro and Chauhan, Ganesh and Athanasiu, Lavinia and Renter{\'\i}a, Miguel E and Kim, Sungeun and Hoehn, David and Armstrong, Nicola J and Chen, Qiang and Holmes, Avram J and den Braber, Anouk and Kloszewska, Iwona and Andersson, Micael and Espeseth, Thomas and Grimm, Oliver and Abramovic, Lucija and Alhusaini, Saud and Milaneschi, Yuri and Papmeyer, Martina and Axelsson, Tomas and Ehrlich, Stefan and Roiz-Santia{\~n}ez, Roberto and Kraemer, Bernd and H{\r a}berg, Asta K and Jones, Hannah J and Pike, G Bruce and Stein, Dan J and Stevens, Allison and Bralten, Janita and Vernooij, Meike W and Harris, Tamara B and Filippi, Irina and Witte, A Veronica and Guadalupe, Tulio and Wittfeld, Katharina and Mosley, Thomas H and Becker, James T and Doan, Nhat Trung and Hagenaars, Saskia P and Saba, Yasaman and Cuellar-Partida, Gabriel and Amin, Najaf and Hilal, Saima and Nho, Kwangsik and Mirza-Schreiber, Nazanin and Arfanakis, Konstantinos and Becker, Diane M and Ames, David and Goldman, Aaron L and Lee, Phil H and Boomsma, Dorret I and Lovestone, Simon and Giddaluru, Sudheer and Le Hellard, Stephanie and Mattheisen, Manuel and Bohlken, Marc M and Kasperaviciute, Dalia and Schmaal, Lianne and Lawrie, Stephen M and Agartz, Ingrid and Walton, Esther and Tordesillas-Gutierrez, Diana and Davies, Gareth E and Shin, Jean and Ipser, Jonathan C and Vinke, Louis N and Hoogman, Martine and Jia, Tianye and Burkhardt, Ralph and Klein, Marieke and Crivello, Fabrice and Janowitz, Deborah and Carmichael, Owen and Haukvik, Unn K and Aribisala, Benjamin S and Schmidt, Helena and Strike, Lachlan T and Cheng, Ching-Yu and Risacher, Shannon L and P{\"u}tz, Benno and Fleischman, Debra A and Assareh, Amelia A and Mattay, Venkata S and Buckner, Randy L and Mecocci, Patrizia and Dale, Anders M and Cichon, Sven and Boks, Marco P and Matarin, Mar and Penninx, Brenda W J H and Calhoun, Vince D and Chakravarty, M Mallar and Marquand, Andre F and Macare, Christine and Kharabian Masouleh, Shahrzad and Oosterlaan, Jaap and Amouyel, Philippe and Hegenscheid, Katrin and Rotter, Jerome I and Schork, Andrew J and Liewald, David C M and de Zubicaray, Greig I and Wong, Tien Yin and Shen, Li and S{\"a}mann, Philipp G and Brodaty, Henry and Roffman, Joshua L and de Geus, Eco J C and Tsolaki, Magda and Erk, Susanne and van Eijk, Kristel R and Cavalleri, Gianpiero L and van der Wee, Nic J A and McIntosh, Andrew M and Gollub, Randy L and Bulayeva, Kazima B and Bernard, Manon and Richards, Jennifer S and Himali, Jayandra J and Loeffler, Markus and Rommelse, Nanda and Hoffmann, Wolfgang and Westlye, Lars T and Vald{\'e}s Hern{\'a}ndez, Maria C and Hansell, Narelle K and van Erp, Theo G M and Wolf, Christiane and Kwok, John B J and Vellas, Bruno and Heinz, Andreas and Olde Loohuis, Loes M and Delanty, Norman and Ho, Beng-Choon and Ching, Christopher R K and Shumskaya, Elena and Singh, Baljeet and Hofman, Albert and van der Meer, Dennis and Homuth, Georg and Psaty, Bruce M and Bastin, Mark E and Montgomery, Grant W and Foroud, Tatiana M and Reppermund, Simone and Hottenga, Jouke-Jan and Simmons, Andrew and Meyer-Lindenberg, Andreas and Cahn, Wiepke and Whelan, Christopher D and van Donkelaar, Marjolein M J and Yang, Qiong and Hosten, Norbert and Green, Robert C and Thalamuthu, Anbupalam and Mohnke, Sebastian and Hulshoff Pol, Hilleke E and Lin, Honghuang and Jack, Clifford R and Schofield, Peter R and M{\"u}hleisen, Thomas W and Maillard, Pauline and Potkin, Steven G and Wen, Wei and Fletcher, Evan and Toga, Arthur W and Gruber, Oliver and Huentelman, Matthew and Davey Smith, George and Launer, Lenore J and Nyberg, Lars and J{\"o}nsson, Erik G and Crespo-Facorro, Benedicto and Koen, Nastassja and Greve, Douglas N and Uitterlinden, Andr{\'e} G and Weinberger, Daniel R and Steen, Vidar M and Fedko, Iryna O and Groenewold, Nynke A and Niessen, Wiro J and Toro, Roberto and Tzourio, Christophe and Longstreth, William T and Ikram, M Kamran and Smoller, Jordan W and van Tol, Marie-Jose and Sussmann, Jessika E and Paus, Tom{\'a}{\v s} and Lema{\^\i}tre, Herv{\'e} and Schroeter, Matthias L and Mazoyer, Bernard and Andreassen, Ole A and Holsboer, Florian and Depondt, Chantal and Veltman, Dick J and Turner, Jessica A and Pausova, Zdenka and Schumann, Gunter and van Rooij, Daan and Djurovic, Srdjan and Deary, Ian J and McMahon, Katie L and M{\"u}ller-Myhsok, Bertram and Brouwer, Rachel M and Soininen, Hilkka and Pandolfo, Massimo and Wassink, Thomas H and Cheung, Joshua W and Wolfers, Thomas and Martinot, Jean-Luc and Zwiers, Marcel P and Nauck, Matthias and Melle, Ingrid and Martin, Nicholas G and Kanai, Ryota and Westman, Eric and Kahn, Ren{\'e} S and Sisodiya, Sanjay M and White, Tonya and Saremi, Arvin and van Bokhoven, Hans and Brunner, Han G and V{\"o}lzke, Henry and Wright, Margaret J and van {\textquoteright}t Ent, Dennis and N{\"o}then, Markus M and Ophoff, Roel A and Buitelaar, Jan K and Fern{\'a}ndez, Guill{\'e}n and Sachdev, Perminder S and Rietschel, Marcella and van Haren, Neeltje E M and Fisher, Simon E and Beiser, Alexa S and Francks, Clyde and Saykin, Andrew J and Mather, Karen A and Romanczuk-Seiferth, Nina and Hartman, Catharina A and DeStefano, Anita L and Heslenfeld, Dirk J and Weiner, Michael W and Walter, Henrik and Hoekstra, Pieter J and Nyquist, Paul A and Franke, Barbara and Bennett, David A and Grabe, Hans J and Johnson, Andrew D and Chen, Christopher and van Duijn, Cornelia M and Lopez, Oscar L and Fornage, Myriam and Wardlaw, Joanna M and Schmidt, Reinhold and DeCarli, Charles and De Jager, Philip L and Villringer, Arno and Debette, Stephanie and Gudnason, Vilmundur and Medland, Sarah E and Shulman, Joshua M and Thompson, Paul M and Seshadri, Sudha and Ikram, M Arfan} } @article {8207, title = {Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.}, journal = {Nat Genet}, volume = {51}, year = {2019}, month = {2019 Oct}, pages = {1459-1474}, abstract = {

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.

}, issn = {1546-1718}, doi = {10.1038/s41588-019-0504-x}, author = {Tin, Adrienne and Marten, Jonathan and Halperin Kuhns, Victoria L and Li, Yong and Wuttke, Matthias and Kirsten, Holger and Sieber, Karsten B and Qiu, Chengxiang and Gorski, Mathias and Yu, Zhi and Giri, Ayush and Sveinbjornsson, Gardar and Li, Man and Chu, Audrey Y and Hoppmann, Anselm and O{\textquoteright}Connor, Luke J and Prins, Bram and Nutile, Teresa and Noce, Damia and Akiyama, Masato and Cocca, Massimiliano and Ghasemi, Sahar and van der Most, Peter J and Horn, Katrin and Xu, Yizhe and Fuchsberger, Christian and Sedaghat, Sanaz and Afaq, Saima and Amin, Najaf and Arnl{\"o}v, Johan and Bakker, Stephan J L and Bansal, Nisha and Baptista, Daniela and Bergmann, Sven and Biggs, Mary L and Biino, Ginevra and Boerwinkle, Eric and Bottinger, Erwin P and Boutin, Thibaud S and Brumat, Marco and Burkhardt, Ralph and Campana, Eric and Campbell, Archie and Campbell, Harry and Carroll, Robert J and Catamo, Eulalia and Chambers, John C and Ciullo, Marina and Concas, Maria Pina and Coresh, Josef and Corre, Tanguy and Cusi, Daniele and Felicita, Sala Cinzia and de Borst, Martin H and De Grandi, Alessandro and de Mutsert, Ren{\'e}e and de Vries, Aiko P J and Delgado, Graciela and Demirkan, Ayse and Devuyst, Olivier and Dittrich, Katalin and Eckardt, Kai-Uwe and Ehret, Georg and Endlich, Karlhans and Evans, Michele K and Gansevoort, Ron T and Gasparini, Paolo and Giedraitis, Vilmantas and Gieger, Christian and Girotto, Giorgia and G{\"o}gele, Martin and Gordon, Scott D and Gudbjartsson, Daniel F and Gudnason, Vilmundur and Haller, Toomas and Hamet, Pavel and Harris, Tamara B and Hayward, Caroline and Hicks, Andrew A and Hofer, Edith and Holm, Hilma and Huang, Wei and Hutri-K{\"a}h{\"o}nen, Nina and Hwang, Shih-Jen and Ikram, M Arfan and Lewis, Raychel M and Ingelsson, Erik and Jakobsdottir, Johanna and Jonsdottir, Ingileif and Jonsson, Helgi and Joshi, Peter K and Josyula, Navya Shilpa and Jung, Bettina and K{\"a}h{\"o}nen, Mika and Kamatani, Yoichiro and Kanai, Masahiro and Kerr, Shona M and Kiess, Wieland and Kleber, Marcus E and Koenig, Wolfgang and Kooner, Jaspal S and K{\"o}rner, Antje and Kovacs, Peter and Kr{\"a}mer, Bernhard K and Kronenberg, Florian and Kubo, Michiaki and Kuhnel, Brigitte and La Bianca, Martina and Lange, Leslie A and Lehne, Benjamin and Lehtim{\"a}ki, Terho and Liu, Jun and Loeffler, Markus and Loos, Ruth J F and Lyytik{\"a}inen, Leo-Pekka and M{\"a}gi, Reedik and Mahajan, Anubha and Martin, Nicholas G and M{\"a}rz, Winfried and Mascalzoni, Deborah and Matsuda, Koichi and Meisinger, Christa and Meitinger, Thomas and Metspalu, Andres and Milaneschi, Yuri and O{\textquoteright}Donnell, Christopher J and Wilson, Otis D and Gaziano, J Michael and Mishra, Pashupati P and Mohlke, Karen L and Mononen, Nina and Montgomery, Grant W and Mook-Kanamori, Dennis O and M{\"u}ller-Nurasyid, Martina and Nadkarni, Girish N and Nalls, Mike A and Nauck, Matthias and Nikus, Kjell and Ning, Boting and Nolte, Ilja M and Noordam, Raymond and O{\textquoteright}Connell, Jeffrey R and Olafsson, Isleifur and Padmanabhan, Sandosh and Penninx, Brenda W J H and Perls, Thomas and Peters, Annette and Pirastu, Mario and Pirastu, Nicola and Pistis, Giorgio and Polasek, Ozren and Ponte, Belen and Porteous, David J and Poulain, Tanja and Preuss, Michael H and Rabelink, Ton J and Raffield, Laura M and Raitakari, Olli T and Rettig, Rainer and Rheinberger, Myriam and Rice, Kenneth M and Rizzi, Federica and Robino, Antonietta and Rudan, Igor and Krajcoviechova, Alena and Cifkova, Renata and Rueedi, Rico and Ruggiero, Daniela and Ryan, Kathleen A and Saba, Yasaman and Salvi, Erika and Schmidt, Helena and Schmidt, Reinhold and Shaffer, Christian M and Smith, Albert V and Smith, Blair H and Spracklen, Cassandra N and Strauch, Konstantin and Stumvoll, Michael and Sulem, Patrick and Tajuddin, Salman M and Teren, Andrej and Thiery, Joachim and Thio, Chris H L and Thorsteinsdottir, Unnur and Toniolo, Daniela and T{\"o}njes, Anke and Tremblay, Johanne and Uitterlinden, Andr{\'e} G and Vaccargiu, Simona and van der Harst, Pim and van Duijn, Cornelia M and Verweij, Niek and V{\"o}lker, Uwe and Vollenweider, Peter and Waeber, G{\'e}rard and Waldenberger, Melanie and Whitfield, John B and Wild, Sarah H and Wilson, James F and Yang, Qiong and Zhang, Weihua and Zonderman, Alan B and Bochud, Murielle and Wilson, James G and Pendergrass, Sarah A and Ho, Kevin and Parsa, Afshin and Pramstaller, Peter P and Psaty, Bruce M and B{\"o}ger, Carsten A and Snieder, Harold and Butterworth, Adam S and Okada, Yukinori and Edwards, Todd L and Stefansson, Kari and Susztak, Katalin and Scholz, Markus and Heid, Iris M and Hung, Adriana M and Teumer, Alexander and Pattaro, Cristian and Woodward, Owen M and Vitart, Veronique and K{\"o}ttgen, Anna} } @article {8835, title = {Genetic insights into biological mechanisms governing human ovarian ageing.}, journal = {Nature}, volume = {596}, year = {2021}, month = {2021 Aug}, pages = {393-397}, abstract = {

Reproductive longevity is essential for fertility and influences healthy ageing in women, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1\% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.

}, issn = {1476-4687}, doi = {10.1038/s41586-021-03779-7}, author = {Ruth, Katherine S and Day, Felix R and Hussain, Jazib and Mart{\'\i}nez-Marchal, Ana and Aiken, Catherine E and Azad, Ajuna and Thompson, Deborah J and Knoblochova, Lucie and Abe, Hironori and Tarry-Adkins, Jane L and Gonzalez, Javier Martin and Fontanillas, Pierre and Claringbould, Annique and Bakker, Olivier B and Sulem, Patrick and Walters, Robin G and Terao, Chikashi and Turon, Sandra and Horikoshi, Momoko and Lin, Kuang and Onland-Moret, N Charlotte and Sankar, Aditya and Hertz, Emil Peter Thrane and Timshel, Pascal N and Shukla, Vallari and Borup, Rehannah and Olsen, Kristina W and Aguilera, Paula and Ferrer-Roda, M{\`o}nica and Huang, Yan and Stankovic, Stasa and Timmers, Paul R H J and Ahearn, Thomas U and Alizadeh, Behrooz Z and Naderi, Elnaz and Andrulis, Irene L and Arnold, Alice M and Aronson, Kristan J and Augustinsson, Annelie and Bandinelli, Stefania and Barbieri, Caterina M and Beaumont, Robin N and Becher, Heiko and Beckmann, Matthias W and Benonisdottir, Stefania and Bergmann, Sven and Bochud, Murielle and Boerwinkle, Eric and Bojesen, Stig E and Bolla, Manjeet K and Boomsma, Dorret I and Bowker, Nicholas and Brody, Jennifer A and Broer, Linda and Buring, Julie E and Campbell, Archie and Campbell, Harry and Castelao, Jose E and Catamo, Eulalia and Chanock, Stephen J and Chenevix-Trench, Georgia and Ciullo, Marina and Corre, Tanguy and Couch, Fergus J and Cox, Angela and Crisponi, Laura and Cross, Simon S and Cucca, Francesco and Czene, Kamila and Smith, George Davey and de Geus, Eco J C N and de Mutsert, Ren{\'e}e and De Vivo, Immaculata and Demerath, Ellen W and Dennis, Joe and Dunning, Alison M and Dwek, Miriam and Eriksson, Mikael and Esko, T{\~o}nu and Fasching, Peter A and Faul, Jessica D and Ferrucci, Luigi and Franceschini, Nora and Frayling, Timothy M and Gago-Dominguez, Manuela and Mezzavilla, Massimo and Garc{\'\i}a-Closas, Montserrat and Gieger, Christian and Giles, Graham G and Grallert, Harald and Gudbjartsson, Daniel F and Gudnason, Vilmundur and Gu{\'e}nel, Pascal and Haiman, Christopher A and H{\r a}kansson, Niclas and Hall, Per and Hayward, Caroline and He, Chunyan and He, Wei and Heiss, Gerardo and H{\o}ffding, Miya K and Hopper, John L and Hottenga, Jouke J and Hu, Frank and Hunter, David and Ikram, Mohammad A and Jackson, Rebecca D and Joaquim, Micaella D R and John, Esther M and Joshi, Peter K and Karasik, David and Kardia, Sharon L R and Kartsonaki, Christiana and Karlsson, Robert and Kitahara, Cari M and Kolcic, Ivana and Kooperberg, Charles and Kraft, Peter and Kurian, Allison W and Kutalik, Zolt{\'a}n and La Bianca, Martina and Lachance, Genevieve and Langenberg, Claudia and Launer, Lenore J and Laven, Joop S E and Lawlor, Deborah A and Le Marchand, Lo{\"\i}c and Li, Jingmei and Lindblom, Annika and Lindstr{\"o}m, Sara and Lindstrom, Tricia and Linet, Martha and Liu, Yongmei and Liu, Simin and Luan, Jian{\textquoteright}an and M{\"a}gi, Reedik and Magnusson, Patrik K E and Mangino, Massimo and Mannermaa, Arto and Marco, Brumat and Marten, Jonathan and Martin, Nicholas G and Mbarek, Hamdi and McKnight, Barbara and Medland, Sarah E and Meisinger, Christa and Meitinger, Thomas and Menni, Cristina and Metspalu, Andres and Milani, Lili and Milne, Roger L and Montgomery, Grant W and Mook-Kanamori, Dennis O and Mulas, Antonella and Mulligan, Anna M and Murray, Alison and Nalls, Mike A and Newman, Anne and Noordam, Raymond and Nutile, Teresa and Nyholt, Dale R and Olshan, Andrew F and Olsson, H{\r a}kan and Painter, Jodie N and Patel, Alpa V and Pedersen, Nancy L and Perjakova, Natalia and Peters, Annette and Peters, Ulrike and Pharoah, Paul D P and Polasek, Ozren and Porcu, Eleonora and Psaty, Bruce M and Rahman, Iffat and Rennert, Gad and Rennert, Hedy S and Ridker, Paul M and Ring, Susan M and Robino, Antonietta and Rose, Lynda M and Rosendaal, Frits R and Rossouw, Jacques and Rudan, Igor and Rueedi, Rico and Ruggiero, Daniela and Sala, Cinzia F and Saloustros, Emmanouil and Sandler, Dale P and Sanna, Serena and Sawyer, Elinor J and Sarnowski, Chloe and Schlessinger, David and Schmidt, Marjanka K and Schoemaker, Minouk J and Schraut, Katharina E and Scott, Christopher and Shekari, Saleh and Shrikhande, Amruta and Smith, Albert V and Smith, Blair H and Smith, Jennifer A and Sorice, Rossella and Southey, Melissa C and Spector, Tim D and Spinelli, John J and Stampfer, Meir and St{\"o}ckl, Doris and van Meurs, Joyce B J and Strauch, Konstantin and Styrkarsdottir, Unnur and Swerdlow, Anthony J and Tanaka, Toshiko and Teras, Lauren R and Teumer, Alexander and {\TH}orsteinsdottir, Unnur and Timpson, Nicholas J and Toniolo, Daniela and Traglia, Michela and Troester, Melissa A and Truong, Th{\'e}r{\`e}se and Tyrrell, Jessica and Uitterlinden, Andr{\'e} G and Ulivi, Sheila and Vachon, Celine M and Vitart, Veronique and V{\"o}lker, Uwe and Vollenweider, Peter and V{\"o}lzke, Henry and Wang, Qin and Wareham, Nicholas J and Weinberg, Clarice R and Weir, David R and Wilcox, Amber N and van Dijk, Ko Willems and Willemsen, Gonneke and Wilson, James F and Wolffenbuttel, Bruce H R and Wolk, Alicja and Wood, Andrew R and Zhao, Wei and Zygmunt, Marek and Chen, Zhengming and Li, Liming and Franke, Lude and Burgess, Stephen and Deelen, Patrick and Pers, Tune H and Gr{\o}ndahl, Marie Louise and Andersen, Claus Yding and Pujol, Anna and Lopez-Contreras, Andres J and Daniel, Jeremy A and Stefansson, Kari and Chang-Claude, Jenny and van der Schouw, Yvonne T and Lunetta, Kathryn L and Chasman, Daniel I and Easton, Douglas F and Visser, Jenny A and Ozanne, Susan E and Namekawa, Satoshi H and Solc, Petr and Murabito, Joanne M and Ong, Ken K and Hoffmann, Eva R and Murray, Anna and Roig, Ignasi and Perry, John R B} } @article {9112, title = {Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.}, journal = {Commun Biol}, volume = {5}, year = {2022}, month = {2022 Jun 13}, pages = {580}, abstract = {

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n = 178,691, n = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.

}, keywords = {Creatinine, Diabetes Mellitus, Diabetic Nephropathies, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney}, issn = {2399-3642}, doi = {10.1038/s42003-022-03448-z}, author = {Winkler, Thomas W and Rasheed, Humaira and Teumer, Alexander and Gorski, Mathias and Rowan, Bryce X and Stanzick, Kira J and Thomas, Laurent F and Tin, Adrienne and Hoppmann, Anselm and Chu, Audrey Y and Tayo, Bamidele and Thio, Chris H L and Cusi, Daniele and Chai, Jin-Fang and Sieber, Karsten B and Horn, Katrin and Li, Man and Scholz, Markus and Cocca, Massimiliano and Wuttke, Matthias and van der Most, Peter J and Yang, Qiong and Ghasemi, Sahar and Nutile, Teresa and Li, Yong and Pontali, Giulia and G{\"u}nther, Felix and Dehghan, Abbas and Correa, Adolfo and Parsa, Afshin and Feresin, Agnese and de Vries, Aiko P J and Zonderman, Alan B and Smith, Albert V and Oldehinkel, Albertine J and De Grandi, Alessandro and Rosenkranz, Alexander R and Franke, Andre and Teren, Andrej and Metspalu, Andres and Hicks, Andrew A and Morris, Andrew P and T{\"o}njes, Anke and Morgan, Anna and Podgornaia, Anna I and Peters, Annette and K{\"o}rner, Antje and Mahajan, Anubha and Campbell, Archie and Freedman, Barry I and Spedicati, Beatrice and Ponte, Belen and Sch{\"o}ttker, Ben and Brumpton, Ben and Banas, Bernhard and Kr{\"a}mer, Bernhard K and Jung, Bettina and {\r A}svold, Bj{\o}rn Olav and Smith, Blair H and Ning, Boting and Penninx, Brenda W J H and Vanderwerff, Brett R and Psaty, Bruce M and Kammerer, Candace M and Langefeld, Carl D and Hayward, Caroline and Spracklen, Cassandra N and Robinson-Cohen, Cassianne and Hartman, Catharina A and Lindgren, Cecilia M and Wang, Chaolong and Sabanayagam, Charumathi and Heng, Chew-Kiat and Lanzani, Chiara and Khor, Chiea-Chuen and Cheng, Ching-Yu and Fuchsberger, Christian and Gieger, Christian and Shaffer, Christian M and Schulz, Christina-Alexandra and Willer, Cristen J and Chasman, Daniel I and Gudbjartsson, Daniel F and Ruggiero, Daniela and Toniolo, Daniela and Czamara, Darina and Porteous, David J and Waterworth, Dawn M and Mascalzoni, Deborah and Mook-Kanamori, Dennis O and Reilly, Dermot F and Daw, E Warwick and Hofer, Edith and Boerwinkle, Eric and Salvi, Erika and Bottinger, Erwin P and Tai, E-Shyong and Catamo, Eulalia and Rizzi, Federica and Guo, Feng and Rivadeneira, Fernando and Guilianini, Franco and Sveinbjornsson, Gardar and Ehret, Georg and Waeber, G{\'e}rard and Biino, Ginevra and Girotto, Giorgia and Pistis, Giorgio and Nadkarni, Girish N and Delgado, Graciela E and Montgomery, Grant W and Snieder, Harold and Campbell, Harry and White, Harvey D and Gao, He and Stringham, Heather M and Schmidt, Helena and Li, Hengtong and Brenner, Hermann and Holm, Hilma and Kirsten, Holgen and Kramer, Holly and Rudan, Igor and Nolte, Ilja M and Tzoulaki, Ioanna and Olafsson, Isleifur and Martins, Jade and Cook, James P and Wilson, James F and Halbritter, Jan and Felix, Janine F and Divers, Jasmin and Kooner, Jaspal S and Lee, Jeannette Jen-Mai and O{\textquoteright}Connell, Jeffrey and Rotter, Jerome I and Liu, Jianjun and Xu, Jie and Thiery, Joachim and Arnl{\"o}v, Johan and Kuusisto, Johanna and Jakobsdottir, Johanna and Tremblay, Johanne and Chambers, John C and Whitfield, John B and Gaziano, John M and Marten, Jonathan and Coresh, Josef and Jonas, Jost B and Mychaleckyj, Josyf C and Christensen, Kaare and Eckardt, Kai-Uwe and Mohlke, Karen L and Endlich, Karlhans and Dittrich, Katalin and Ryan, Kathleen A and Rice, Kenneth M and Taylor, Kent D and Ho, Kevin and Nikus, Kjell and Matsuda, Koichi and Strauch, Konstantin and Miliku, Kozeta and Hveem, Kristian and Lind, Lars and Wallentin, Lars and Yerges-Armstrong, Laura M and Raffield, Laura M and Phillips, Lawrence S and Launer, Lenore J and Lyytik{\"a}inen, Leo-Pekka and Lange, Leslie A and Citterio, Lorena and Klaric, Lucija and Ikram, M Arfan and Ising, Marcus and Kleber, Marcus E and Francescatto, Margherita and Concas, Maria Pina and Ciullo, Marina and Piratsu, Mario and Orho-Melander, Marju and Laakso, Markku and Loeffler, Markus and Perola, Markus and de Borst, Martin H and G{\"o}gele, Martin and Bianca, Martina La and Lukas, Mary Ann and Feitosa, Mary F and Biggs, Mary L and Wojczynski, Mary K and Kavousi, Maryam and Kanai, Masahiro and Akiyama, Masato and Yasuda, Masayuki and Nauck, Matthias and Waldenberger, Melanie and Chee, Miao-Li and Chee, Miao-Ling and Boehnke, Michael and Preuss, Michael H and Stumvoll, Michael and Province, Michael A and Evans, Michele K and O{\textquoteright}Donoghue, Michelle L and Kubo, Michiaki and K{\"a}h{\"o}nen, Mika and Kastarinen, Mika and Nalls, Mike A and Kuokkanen, Mikko and Ghanbari, Mohsen and Bochud, Murielle and Josyula, Navya Shilpa and Martin, Nicholas G and Tan, Nicholas Y Q and Palmer, Nicholette D and Pirastu, Nicola and Schupf, Nicole and Verweij, Niek and Hutri-K{\"a}h{\"o}nen, Nina and Mononen, Nina and Bansal, Nisha and Devuyst, Olivier and Melander, Olle and Raitakari, Olli T and Polasek, Ozren and Manunta, Paolo and Gasparini, Paolo and Mishra, Pashupati P and Sulem, Patrick and Magnusson, Patrik K E and Elliott, Paul and Ridker, Paul M and Hamet, Pavel and Svensson, Per O and Joshi, Peter K and Kovacs, Peter and Pramstaller, Peter P and Rossing, Peter and Vollenweider, Peter and van der Harst, Pim and Dorajoo, Rajkumar and Sim, Ralene Z H and Burkhardt, Ralph and Tao, Ran and Noordam, Raymond and M{\"a}gi, Reedik and Schmidt, Reinhold and de Mutsert, Ren{\'e}e and Rueedi, Rico and van Dam, Rob M and Carroll, Robert J and Gansevoort, Ron T and Loos, Ruth J F and Felicita, Sala Cinzia and Sedaghat, Sanaz and Padmanabhan, Sandosh and Freitag-Wolf, Sandra and Pendergrass, Sarah A and Graham, Sarah E and Gordon, Scott D and Hwang, Shih-Jen and Kerr, Shona M and Vaccargiu, Simona and Patil, Snehal B and Hallan, Stein and Bakker, Stephan J L and Lim, Su-Chi and Lucae, Susanne and Vogelezang, Suzanne and Bergmann, Sven and Corre, Tanguy and Ahluwalia, Tarunveer S and Lehtim{\"a}ki, Terho and Boutin, Thibaud S and Meitinger, Thomas and Wong, Tien-Yin and Bergler, Tobias and Rabelink, Ton J and Esko, T{\~o}nu and Haller, Toomas and Thorsteinsdottir, Unnur and V{\"o}lker, Uwe and Foo, Valencia Hui Xian and Salomaa, Veikko and Vitart, Veronique and Giedraitis, Vilmantas and Gudnason, Vilmundur and Jaddoe, Vincent W V and Huang, Wei and Zhang, Weihua and Wei, Wen Bin and Kiess, Wieland and M{\"a}rz, Winfried and Koenig, Wolfgang and Lieb, Wolfgang and G{\`a}o, Xin and Sim, Xueling and Wang, Ya Xing and Friedlander, Yechiel and Tham, Yih-Chung and Kamatani, Yoichiro and Okada, Yukinori and Milaneschi, Yuri and Yu, Zhi and Stark, Klaus J and Stefansson, Kari and B{\"o}ger, Carsten A and Hung, Adriana M and Kronenberg, Florian and K{\"o}ttgen, Anna and Pattaro, Cristian and Heid, Iris M} } @article {9579, title = {X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements.}, journal = {Nat Commun}, volume = {15}, year = {2024}, month = {2024 Jan 18}, pages = {586}, abstract = {

X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.

}, keywords = {Androgens, Chromosomes, Human, X, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kidney, Male, Polymorphism, Single Nucleotide, Response Elements, Tetraspanins}, issn = {2041-1723}, doi = {10.1038/s41467-024-44709-1}, author = {Scholz, Markus and Horn, Katrin and Pott, Janne and Wuttke, Matthias and K{\"u}hnapfel, Andreas and Nasr, M Kamal and Kirsten, Holger and Li, Yong and Hoppmann, Anselm and Gorski, Mathias and Ghasemi, Sahar and Li, Man and Tin, Adrienne and Chai, Jin-Fang and Cocca, Massimiliano and Wang, Judy and Nutile, Teresa and Akiyama, Masato and {\r A}svold, Bj{\o}rn Olav and Bansal, Nisha and Biggs, Mary L and Boutin, Thibaud and Brenner, Hermann and Brumpton, Ben and Burkhardt, Ralph and Cai, Jianwen and Campbell, Archie and Campbell, Harry and Chalmers, John and Chasman, Daniel I and Chee, Miao Ling and Chee, Miao Li and Chen, Xu and Cheng, Ching-Yu and Cifkova, Renata and Daviglus, Martha and Delgado, Graciela and Dittrich, Katalin and Edwards, Todd L and Endlich, Karlhans and Michael Gaziano, J and Giri, Ayush and Giulianini, Franco and Gordon, Scott D and Gudbjartsson, Daniel F and Hallan, Stein and Hamet, Pavel and Hartman, Catharina A and Hayward, Caroline and Heid, Iris M and Hellwege, Jacklyn N and Holleczek, Bernd and Holm, Hilma and Hutri-K{\"a}h{\"o}nen, Nina and Hveem, Kristian and Isermann, Berend and Jonas, Jost B and Joshi, Peter K and Kamatani, Yoichiro and Kanai, Masahiro and Kastarinen, Mika and Khor, Chiea Chuen and Kiess, Wieland and Kleber, Marcus E and K{\"o}rner, Antje and Kovacs, Peter and Krajcoviechova, Alena and Kramer, Holly and Kr{\"a}mer, Bernhard K and Kuokkanen, Mikko and K{\"a}h{\"o}nen, Mika and Lange, Leslie A and Lash, James P and Lehtim{\"a}ki, Terho and Li, Hengtong and Lin, Bridget M and Liu, Jianjun and Loeffler, Markus and Lyytik{\"a}inen, Leo-Pekka and Magnusson, Patrik K E and Martin, Nicholas G and Matsuda, Koichi and Milaneschi, Yuri and Mishra, Pashupati P and Mononen, Nina and Montgomery, Grant W and Mook-Kanamori, Dennis O and Mychaleckyj, Josyf C and M{\"a}rz, Winfried and Nauck, Matthias and Nikus, Kjell and Nolte, Ilja M and Noordam, Raymond and Okada, Yukinori and Olafsson, Isleifur and Oldehinkel, Albertine J and Penninx, Brenda W J H and Perola, Markus and Pirastu, Nicola and Polasek, Ozren and Porteous, David J and Poulain, Tanja and Psaty, Bruce M and Rabelink, Ton J and Raffield, Laura M and Raitakari, Olli T and Rasheed, Humaira and Reilly, Dermot F and Rice, Kenneth M and Richmond, Anne and Ridker, Paul M and Rotter, Jerome I and Rudan, Igor and Sabanayagam, Charumathi and Salomaa, Veikko and Schneiderman, Neil and Sch{\"o}ttker, Ben and Sims, Mario and Snieder, Harold and Stark, Klaus J and Stefansson, Kari and Stocker, Hannah and Stumvoll, Michael and Sulem, Patrick and Sveinbjornsson, Gardar and Svensson, Per O and Tai, E-Shyong and Taylor, Kent D and Tayo, Bamidele O and Teren, Andrej and Tham, Yih-Chung and Thiery, Joachim and Thio, Chris H L and Thomas, Laurent F and Tremblay, Johanne and T{\"o}njes, Anke and van der Most, Peter J and Vitart, Veronique and V{\"o}lker, Uwe and Wang, Ya Xing and Wang, Chaolong and Wei, Wen Bin and Whitfield, John B and Wild, Sarah H and Wilson, James F and Winkler, Thomas W and Wong, Tien-Yin and Woodward, Mark and Sim, Xueling and Chu, Audrey Y and Feitosa, Mary F and Thorsteinsdottir, Unnur and Hung, Adriana M and Teumer, Alexander and Franceschini, Nora and Parsa, Afshin and K{\"o}ttgen, Anna and Schlosser, Pascal and Pattaro, Cristian} }