@article {6089, title = {Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation.}, journal = {Blood}, volume = {120}, year = {2012}, month = {2012 Dec 06}, pages = {4873-81}, abstract = {

We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (P < 5 {\texttimes} 10(-8)) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association. We confirmed the association of the 4G/5G proxy SNP rs2227631 in the promoter region of SERPINE1 (7q22.1) and discovered genome-wide significant associations at 3 additional loci: chromosome 7q22.1 close to SERPINE1 (rs6976053, discovery P = 3.4 {\texttimes} 10(-10)); chromosome 11p15.2 within ARNTL (rs6486122, discovery P = 3.0 {\texttimes} 10(-8)); and chromosome 3p25.2 within PPARG (rs11128603, discovery P = 2.9 {\texttimes} 10(-8)). Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal association with type 2 diabetes and coronary artery disease at ARNTL (P < .05). Functional studies identified MUC3 as a candidate gene for the second association signal on 7q22.1. In summary, SNPs in SERPINE1 and ARNTL and an SNP associated with the expression of MUC3 were robustly associated with circulating levels of PAI-1.

}, keywords = {Adaptor Proteins, Signal Transducing, ARNTL Transcription Factors, ATPases Associated with Diverse Cellular Activities, Cell Line, Cell Line, Tumor, Cohort Studies, Coronary Artery Disease, Diabetes Mellitus, Type 2, Gene Expression Profiling, Gene Expression Regulation, Gene Frequency, Genome-Wide Association Study, Genotype, Humans, LIM Domain Proteins, Meta-Analysis as Topic, Monocytes, Mucin-3, Plasminogen Activator Inhibitor 1, Polymorphism, Single Nucleotide, PPAR gamma, Proteasome Endopeptidase Complex, RNA Interference, Transcription Factors}, issn = {1528-0020}, doi = {10.1182/blood-2012-06-436188}, author = {Huang, Jie and Sabater-Lleal, Maria and Asselbergs, Folkert W and Tregouet, David and Shin, So-Youn and Ding, Jingzhong and Baumert, Jens and Oudot-Mellakh, Tiphaine and Folkersen, Lasse and Johnson, Andrew D and Smith, Nicholas L and Williams, Scott M and Ikram, Mohammad A and Kleber, Marcus E and Becker, Diane M and Truong, Vinh and Mychaleckyj, Josyf C and Tang, Weihong and Yang, Qiong and Sennblad, Bengt and Moore, Jason H and Williams, Frances M K and Dehghan, Abbas and Silbernagel, G{\"u}nther and Schrijvers, Elisabeth M C and Smith, Shelly and Karakas, Mahir and Tofler, Geoffrey H and Silveira, Angela and Navis, Gerjan J and Lohman, Kurt and Chen, Ming-Huei and Peters, Annette and Goel, Anuj and Hopewell, Jemma C and Chambers, John C and Saleheen, Danish and Lundmark, Per and Psaty, Bruce M and Strawbridge, Rona J and Boehm, Bernhard O and Carter, Angela M and Meisinger, Christa and Peden, John F and Bis, Joshua C and McKnight, Barbara and Ohrvik, John and Taylor, Kent and Franzosi, Maria Grazia and Seedorf, Udo and Collins, Rory and Franco-Cereceda, Anders and Syv{\"a}nen, Ann-Christine and Goodall, Alison H and Yanek, Lisa R and Cushman, Mary and M{\"u}ller-Nurasyid, Martina and Folsom, Aaron R and Basu, Saonli and Matijevic, Nena and van Gilst, Wiek H and Kooner, Jaspal S and Hofman, Albert and Danesh, John and Clarke, Robert and Meigs, James B and Kathiresan, Sekar and Reilly, Muredach P and Klopp, Norman and Harris, Tamara B and Winkelmann, Bernhard R and Grant, Peter J and Hillege, Hans L and Watkins, Hugh and Spector, Timothy D and Becker, Lewis C and Tracy, Russell P and M{\"a}rz, Winfried and Uitterlinden, Andr{\'e} G and Eriksson, Per and Cambien, Francois and Morange, Pierre-Emmanuel and Koenig, Wolfgang and Soranzo, Nicole and van der Harst, Pim and Liu, Yongmei and O{\textquoteright}Donnell, Christopher J and Hamsten, Anders} } @article {6091, title = {Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.}, journal = {Nat Genet}, volume = {44}, year = {2012}, month = {2012 Sep}, pages = {991-1005}, abstract = {

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

}, keywords = {Adult, Animals, Blood Glucose, Fasting, Female, Gene Frequency, Genome-Wide Association Study, Humans, Insulin, Male, Metabolic Networks and Pathways, Mice, Osmolar Concentration, Quantitative Trait Loci}, issn = {1546-1718}, doi = {10.1038/ng.2385}, author = {Scott, Robert A and Lagou, Vasiliki and Welch, Ryan P and Wheeler, Eleanor and Montasser, May E and Luan, Jian{\textquoteright}an and M{\"a}gi, Reedik and Strawbridge, Rona J and Rehnberg, Emil and Gustafsson, Stefan and Kanoni, Stavroula and Rasmussen-Torvik, Laura J and Yengo, Loic and Lecoeur, C{\'e}cile and Shungin, Dmitry and Sanna, Serena and Sidore, Carlo and Johnson, Paul C D and Jukema, J Wouter and Johnson, Toby and Mahajan, Anubha and Verweij, Niek and Thorleifsson, Gudmar and Hottenga, Jouke-Jan and Shah, Sonia and Smith, Albert V and Sennblad, Bengt and Gieger, Christian and Salo, Perttu and Perola, Markus and Timpson, Nicholas J and Evans, David M and Pourcain, Beate St and Wu, Ying and Andrews, Jeanette S and Hui, Jennie and Bielak, Lawrence F and Zhao, Wei and Horikoshi, Momoko and Navarro, Pau and Isaacs, Aaron and O{\textquoteright}Connell, Jeffrey R and Stirrups, Kathleen and Vitart, Veronique and Hayward, Caroline and Esko, T{\~o}nu and Mihailov, Evelin and Fraser, Ross M and Fall, Tove and Voight, Benjamin F and Raychaudhuri, Soumya and Chen, Han and Lindgren, Cecilia M and Morris, Andrew P and Rayner, Nigel W and Robertson, Neil and Rybin, Denis and Liu, Ching-Ti and Beckmann, Jacques S and Willems, Sara M and Chines, Peter S and Jackson, Anne U and Kang, Hyun Min and Stringham, Heather M and Song, Kijoung and Tanaka, Toshiko and Peden, John F and Goel, Anuj and Hicks, Andrew A and An, Ping and M{\"u}ller-Nurasyid, Martina and Franco-Cereceda, Anders and Folkersen, Lasse and Marullo, Letizia and Jansen, Hanneke and Oldehinkel, Albertine J and Bruinenberg, Marcel and Pankow, James S and North, Kari E and Forouhi, Nita G and Loos, Ruth J F and Edkins, Sarah and Varga, Tibor V and Hallmans, G{\"o}ran and Oksa, Heikki and Antonella, Mulas and Nagaraja, Ramaiah and Trompet, Stella and Ford, Ian and Bakker, Stephan J L and Kong, Augustine and Kumari, Meena and Gigante, Bruna and Herder, Christian and Munroe, Patricia B and Caulfield, Mark and Antti, Jula and Mangino, Massimo and Small, Kerrin and Miljkovic, Iva and Liu, Yongmei and Atalay, Mustafa and Kiess, Wieland and James, Alan L and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Palmer, Colin N A and Doney, Alex S F and Willemsen, Gonneke and Smit, Johannes H and Campbell, Susan and Polasek, Ozren and Bonnycastle, Lori L and Hercberg, Serge and Dimitriou, Maria and Bolton, Jennifer L and Fowkes, Gerard R and Kovacs, Peter and Lindstr{\"o}m, Jaana and Zemunik, Tatijana and Bandinelli, Stefania and Wild, Sarah H and Basart, Hanneke V and Rathmann, Wolfgang and Grallert, Harald and Maerz, Winfried and Kleber, Marcus E and Boehm, Bernhard O and Peters, Annette and Pramstaller, Peter P and Province, Michael A and Borecki, Ingrid B and Hastie, Nicholas D and Rudan, Igor and Campbell, Harry and Watkins, Hugh and Farrall, Martin and Stumvoll, Michael and Ferrucci, Luigi and Waterworth, Dawn M and Bergman, Richard N and Collins, Francis S and Tuomilehto, Jaakko and Watanabe, Richard M and de Geus, Eco J C and Penninx, Brenda W and Hofman, Albert and Oostra, Ben A and Psaty, Bruce M and Vollenweider, Peter and Wilson, James F and Wright, Alan F and Hovingh, G Kees and Metspalu, Andres and Uusitupa, Matti and Magnusson, Patrik K E and Kyvik, Kirsten O and Kaprio, Jaakko and Price, Jackie F and Dedoussis, George V and Deloukas, Panos and Meneton, Pierre and Lind, Lars and Boehnke, Michael and Shuldiner, Alan R and van Duijn, Cornelia M and Morris, Andrew D and Toenjes, Anke and Peyser, Patricia A and Beilby, John P and K{\"o}rner, Antje and Kuusisto, Johanna and Laakso, Markku and Bornstein, Stefan R and Schwarz, Peter E H and Lakka, Timo A and Rauramaa, Rainer and Adair, Linda S and Smith, George Davey and Spector, Tim D and Illig, Thomas and de Faire, Ulf and Hamsten, Anders and Gudnason, Vilmundur and Kivimaki, Mika and Hingorani, Aroon and Keinanen-Kiukaanniemi, Sirkka M and Saaristo, Timo E and Boomsma, Dorret I and Stefansson, Kari and van der Harst, Pim and Dupuis, Jos{\'e}e and Pedersen, Nancy L and Sattar, Naveed and Harris, Tamara B and Cucca, Francesco and Ripatti, Samuli and Salomaa, Veikko and Mohlke, Karen L and Balkau, Beverley and Froguel, Philippe and Pouta, Anneli and Jarvelin, Marjo-Riitta and Wareham, Nicholas J and Bouatia-Naji, Nabila and McCarthy, Mark I and Franks, Paul W and Meigs, James B and Teslovich, Tanya M and Florez, Jose C and Langenberg, Claudia and Ingelsson, Erik and Prokopenko, Inga and Barroso, In{\^e}s} } @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 {6282, title = {Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia.}, journal = {Hum Mol Genet}, volume = {22}, year = {2013}, month = {2013 Aug 15}, pages = {3381-93}, abstract = {

Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 {\texttimes} 10(-41)) and in 1690 AA subjects (rs505102; P = 1.05 {\texttimes} 10(-8)). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare MPO coding sequence variants that were associated with serum MPO levels (rs28730837, P = 5.21 {\texttimes} 10(-12); rs35897051, P = 3.32 {\texttimes} 10(-8)). A GWAS for plasma MPO levels in 9260 European ancestry subjects identified a chromosome 17q22 region near MPO that was significantly associated (lead SNP rs6503905; P = 2.94 {\texttimes} 10(-12)), but the CFH locus did not exhibit evidence of association with plasma MPO levels. Functional analyses revealed that rs800292 was associated with levels of complement proteins in serum. Variants at chromosome 17q22 also had pleiotropic cis effects on gene expression. In a case-control analysis of \~{}80 000 subjects from CARDIoGRAM, none of the identified single-nucleotide polymorphisms (SNPs) were associated with CAD. These results suggest that distinct genetic factors regulate serum and plasma MPO levels, which may have relevance for various acute and chronic inflammatory disorders. The clinical implications for CAD and a better understanding of the functional basis for the association of CFH and MPO variants with circulating MPO levels require further study.

}, keywords = {Adult, African Americans, Aged, Case-Control Studies, Complement Factor H, Coronary Artery Disease, European Continental Ancestry Group, Female, Gene Expression Regulation, Enzymologic, Genetic Association Studies, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Peroxidase, Polymorphism, Single Nucleotide, Young Adult}, issn = {1460-2083}, doi = {10.1093/hmg/ddt189}, author = {Reiner, Alexander P and Hartiala, Jaana and Zeller, Tanja and Bis, Joshua C and Dupuis, Jos{\'e}e and Fornage, Myriam and Baumert, Jens and Kleber, Marcus E and Wild, Philipp S and Baldus, Stephan and Bielinski, Suzette J and Fontes, Jo{\~a}o D and Illig, Thomas and Keating, Brendan J and Lange, Leslie A and Ojeda, Francisco and M{\"u}ller-Nurasyid, Martina and Munzel, Thomas F and Psaty, Bruce M and Rice, Kenneth and Rotter, Jerome I and Schnabel, Renate B and Tang, W H Wilson and Thorand, Barbara and Erdmann, Jeanette and Jacobs, David R and Wilson, James G and Koenig, Wolfgang and Tracy, Russell P and Blankenberg, Stefan and M{\"a}rz, Winfried and Gross, Myron D and Benjamin, Emelia J and Hazen, Stanley L and Allayee, Hooman} } @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 {6291, title = {Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.}, journal = {PLoS Genet}, volume = {9}, year = {2013}, month = {2013}, pages = {e1003796}, abstract = {

Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in <= 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.

}, keywords = {Animals, Bone and Bones, Bone Density, Calcium, European Continental Ancestry Group, Gene Expression Regulation, Genome-Wide Association Study, Homeostasis, Humans, Kidney, Mice, Polymorphism, Single Nucleotide}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003796}, author = {O{\textquoteright}Seaghdha, Conall M and Wu, Hongsheng and Yang, Qiong and Kapur, Karen and Guessous, Idris and Zuber, Annie Mercier and K{\"o}ttgen, Anna and Stoudmann, Candice and Teumer, Alexander and Kutalik, Zolt{\'a}n and Mangino, Massimo and Dehghan, Abbas and Zhang, Weihua and Eiriksdottir, Gudny and Li, Guo and Tanaka, Toshiko and Portas, Laura and Lopez, Lorna M and Hayward, Caroline and Lohman, Kurt and Matsuda, Koichi and Padmanabhan, Sandosh and Firsov, Dmitri and Sorice, Rossella and Ulivi, Sheila and Brockhaus, A Catharina and Kleber, Marcus E and Mahajan, Anubha and Ernst, Florian D and Gudnason, Vilmundur and Launer, Lenore J and Mace, Aurelien and Boerwinckle, Eric and Arking, Dan E and Tanikawa, Chizu and Nakamura, Yusuke and Brown, Morris J and Gaspoz, Jean-Michel and Theler, Jean-Marc and Siscovick, David S and Psaty, Bruce M and Bergmann, Sven and Vollenweider, Peter and Vitart, Veronique and Wright, Alan F and Zemunik, Tatijana and Boban, Mladen and Kolcic, Ivana and Navarro, Pau and Brown, Edward M and Estrada, Karol and Ding, Jingzhong and Harris, Tamara B and Bandinelli, Stefania and Hernandez, Dena and Singleton, Andrew B and Girotto, Giorgia and Ruggiero, Daniela and d{\textquoteright}Adamo, Adamo Pio and Robino, Antonietta and Meitinger, Thomas and Meisinger, Christa and Davies, Gail and Starr, John M and Chambers, John C and Boehm, Bernhard O and Winkelmann, Bernhard R and Huang, Jie and Murgia, Federico and Wild, Sarah H and Campbell, Harry and Morris, Andrew P and Franco, Oscar H and Hofman, Albert and Uitterlinden, Andr{\'e} G and Rivadeneira, Fernando and V{\"o}lker, Uwe and Hannemann, Anke and Biffar, Reiner and Hoffmann, Wolfgang and Shin, So-Youn and Lescuyer, Pierre and Henry, Hughes and Schurmann, Claudia and Munroe, Patricia B and Gasparini, Paolo and Pirastu, Nicola and Ciullo, Marina and Gieger, Christian and M{\"a}rz, Winfried and Lind, Lars and Spector, Tim D and Smith, Albert V and Rudan, Igor and Wilson, James F and Polasek, Ozren and Deary, Ian J and Pirastu, Mario and Ferrucci, Luigi and Liu, Yongmei and Kestenbaum, Bryan and Kooner, Jaspal S and Witteman, Jacqueline C M and Nauck, Matthias and Kao, W H Linda and Wallaschofski, Henri and Bonny, Olivier and Fox, Caroline S and Bochud, Murielle} } @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 {6367, title = {Genome-wide association study for circulating tissue plasminogen activator levels and functional follow-up implicates endothelial STXBP5 and STX2.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {34}, year = {2014}, month = {2014 May}, pages = {1093-101}, abstract = {

OBJECTIVE: Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide association studies to identify novel correlates of circulating levels of tPA.

APPROACH AND RESULTS: Fourteen cohort studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P<5.0{\texttimes}10(-8)). The first locus is on 6q24.3, with the lead single nucleotide polymorphism (SNP; rs9399599; P=2.9{\texttimes}10(-14)) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739; P=1.3{\texttimes}10(-9)) is intronic to POLB and <200 kb away from the tPA encoding the gene PLAT. We identified a nonsynonymous SNP (rs2020921) in modest linkage disequilibrium with rs3136739 (r(2)=0.50) within exon 5 of PLAT (P=2.0{\texttimes}10(-8)). The third locus is on 12q24.33, with the lead SNP (rs7301826; P=1.0{\texttimes}10(-9)) within intron 7 of STX2. We further found evidence for the association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased the release of tPA from vascular endothelial cells, whereas silencing STX2 increased the tPA release. Through an in silico lookup, we found no associations of the 3 lead SNPs with coronary artery disease or stroke.

CONCLUSIONS: We identified 3 loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release.

}, keywords = {Aged, Cells, Cultured, Coronary Artery Disease, Endothelial Cells, Europe, Female, Gene Expression Regulation, Gene Silencing, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Nerve Tissue Proteins, Phenotype, Polymorphism, Single Nucleotide, R-SNARE Proteins, Risk Factors, Stroke, Syntaxin 1, Tissue Plasminogen Activator, Transfection, United States, Up-Regulation}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.113.302088}, author = {Huang, Jie and Huffman, Jennifer E and Yamakuchi, Munekazu and Yamkauchi, Munekazu and Trompet, Stella and Asselbergs, Folkert W and Sabater-Lleal, Maria and Tr{\'e}gou{\"e}t, David-Alexandre and Chen, Wei-Min and Smith, Nicholas L and Kleber, Marcus E and Shin, So-Youn and Becker, Diane M and Tang, Weihong and Dehghan, Abbas and Johnson, Andrew D and Truong, Vinh and Folkersen, Lasse and Yang, Qiong and Oudot-Mellkah, Tiphaine and Buckley, Brendan M and Moore, Jason H and Williams, Frances M K and Campbell, Harry and Silbernagel, G{\"u}nther and Vitart, Veronique and Rudan, Igor and Tofler, Geoffrey H and Navis, Gerjan J and DeStefano, Anita and Wright, Alan F and Chen, Ming-Huei and de Craen, Anton J M and Worrall, Bradford B and Rudnicka, Alicja R and Rumley, Ann and Bookman, Ebony B and Psaty, Bruce M and Chen, Fang and Keene, Keith L and Franco, Oscar H and B{\"o}hm, Bernhard O and Uitterlinden, Andr{\'e} G and Carter, Angela M and Jukema, J Wouter and Sattar, Naveed and Bis, Joshua C and Ikram, Mohammad A and Sale, Mich{\`e}le M and McKnight, Barbara and Fornage, Myriam and Ford, Ian and Taylor, Kent and Slagboom, P Eline and McArdle, Wendy L and Hsu, Fang-Chi and Franco-Cereceda, Anders and Goodall, Alison H and Yanek, Lisa R and Furie, Karen L and Cushman, Mary and Hofman, Albert and Witteman, Jacqueline C M and Folsom, Aaron R and Basu, Saonli and Matijevic, Nena and van Gilst, Wiek H and Wilson, James F and Westendorp, Rudi G J and Kathiresan, Sekar and Reilly, Muredach P and Tracy, Russell P and Polasek, Ozren and Winkelmann, Bernhard R and Grant, Peter J and Hillege, Hans L and Cambien, Francois and Stott, David J and Lowe, Gordon D and Spector, Timothy D and Meigs, James B and M{\"a}rz, Winfried and Eriksson, Per and Becker, Lewis C and Morange, Pierre-Emmanuel and Soranzo, Nicole and Williams, Scott M and Hayward, Caroline and van der Harst, Pim and Hamsten, Anders and Lowenstein, Charles J and Strachan, David P and O{\textquoteright}Donnell, Christopher J} } @article {7596, title = {Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis.}, journal = {PLoS Med}, volume = {14}, year = {2017}, month = {2017 Sep}, pages = {e1002383}, abstract = {

BACKGROUND: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.

METHODS \& FINDINGS: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95\% CI 1.04-1.06, per HbA1c-raising allele, p = 3 {\texttimes} 10-29); whereas GS-E was not (OR = 1.00, 95\% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11\%) was associated with an absolute decrease in HbA1c of 0.81\%-units (95\% CI 0.66-0.96) per allele in hemizygous men, and 0.68\%-units (95\% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2\% (N = 0.65 million, 95\% CI 0.55-0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.

CONCLUSIONS: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.

}, keywords = {Diabetes Mellitus, Type 2, Genetic Variation, Genome-Wide Association Study, Glycated Hemoglobin A, Humans, Phenotype, Risk}, issn = {1549-1676}, doi = {10.1371/journal.pmed.1002383}, author = {Wheeler, Eleanor and Leong, Aaron and Liu, Ching-Ti and Hivert, Marie-France and Strawbridge, Rona J and Podmore, Clara and Li, Man and Yao, Jie and Sim, Xueling and Hong, Jaeyoung and Chu, Audrey Y and Zhang, Weihua and Wang, Xu and Chen, Peng and Maruthur, Nisa M and Porneala, Bianca C and Sharp, Stephen J and Jia, Yucheng and Kabagambe, Edmond K and Chang, Li-Ching and Chen, Wei-Min and Elks, Cathy E and Evans, Daniel S and Fan, Qiao and Giulianini, Franco and Go, Min Jin and Hottenga, Jouke-Jan and Hu, Yao and Jackson, Anne U and Kanoni, Stavroula and Kim, Young Jin and Kleber, Marcus E and Ladenvall, Claes and Lecoeur, C{\'e}cile and Lim, Sing-Hui and Lu, Yingchang and Mahajan, Anubha and Marzi, Carola and Nalls, Mike A and Navarro, Pau and Nolte, Ilja M and Rose, Lynda M and Rybin, Denis V and Sanna, Serena and Shi, Yuan and Stram, Daniel O and Takeuchi, Fumihiko and Tan, Shu Pei and van der Most, Peter J and van Vliet-Ostaptchouk, Jana V and Wong, Andrew and Yengo, Loic and Zhao, Wanting and Goel, Anuj and Martinez Larrad, Maria Teresa and Radke, D{\"o}rte and Salo, Perttu and Tanaka, Toshiko and van Iperen, Erik P A and Abecasis, Goncalo and Afaq, Saima and Alizadeh, Behrooz Z and Bertoni, Alain G and Bonnefond, Am{\'e}lie and B{\"o}ttcher, Yvonne and Bottinger, Erwin P and Campbell, Harry and Carlson, Olga D and Chen, Chien-Hsiun and Cho, Yoon Shin and Garvey, W Timothy and Gieger, Christian and Goodarzi, Mark O and Grallert, Harald and Hamsten, Anders and Hartman, Catharina A and Herder, Christian and Hsiung, Chao Agnes and Huang, Jie and Igase, Michiya and Isono, Masato and Katsuya, Tomohiro and Khor, Chiea-Chuen and Kiess, Wieland and Kohara, Katsuhiko and Kovacs, Peter and Lee, Juyoung and Lee, Wen-Jane and Lehne, Benjamin and Li, Huaixing and Liu, Jianjun and Lobbens, Stephane and Luan, Jian{\textquoteright}an and Lyssenko, Valeriya and Meitinger, Thomas and Miki, Tetsuro and Miljkovic, Iva and Moon, Sanghoon and Mulas, Antonella and M{\"u}ller, Gabriele and M{\"u}ller-Nurasyid, Martina and Nagaraja, Ramaiah and Nauck, Matthias and Pankow, James S and Polasek, Ozren and Prokopenko, Inga and Ramos, Paula S and Rasmussen-Torvik, Laura and Rathmann, Wolfgang and Rich, Stephen S and Robertson, Neil R and Roden, Michael and Roussel, Ronan and Rudan, Igor and Scott, Robert A and Scott, William R and Sennblad, Bengt and Siscovick, David S and Strauch, Konstantin and Sun, Liang and Swertz, Morris and Tajuddin, Salman M and Taylor, Kent D and Teo, Yik-Ying and Tham, Yih Chung and T{\"o}njes, Anke and Wareham, Nicholas J and Willemsen, Gonneke and Wilsgaard, Tom and Hingorani, Aroon D and Egan, Josephine and Ferrucci, Luigi and Hovingh, G Kees and Jula, Antti and Kivimaki, Mika and Kumari, Meena and Nj{\o}lstad, Inger and Palmer, Colin N A and Serrano R{\'\i}os, Manuel and Stumvoll, Michael and Watkins, Hugh and Aung, Tin and Bl{\"u}her, Matthias and Boehnke, Michael and Boomsma, Dorret I and Bornstein, Stefan R and Chambers, John C and Chasman, Daniel I and Chen, Yii-Der Ida and Chen, Yduan-Tsong and Cheng, Ching-Yu and Cucca, Francesco and de Geus, Eco J C and Deloukas, Panos and Evans, Michele K and Fornage, Myriam and Friedlander, Yechiel and Froguel, Philippe and Groop, Leif and Gross, Myron D and Harris, Tamara B and Hayward, Caroline and Heng, Chew-Kiat and Ingelsson, Erik and Kato, Norihiro and Kim, Bong-Jo and Koh, Woon-Puay and Kooner, Jaspal S and K{\"o}rner, Antje and Kuh, Diana and Kuusisto, Johanna and Laakso, Markku and Lin, Xu and Liu, Yongmei and Loos, Ruth J F and Magnusson, Patrik K E and M{\"a}rz, Winfried and McCarthy, Mark I and Oldehinkel, Albertine J and Ong, Ken K and Pedersen, Nancy L and Pereira, Mark A and Peters, Annette and Ridker, Paul M and Sabanayagam, Charumathi and Sale, Michele and Saleheen, Danish and Saltevo, Juha and Schwarz, Peter Eh and Sheu, Wayne H H and Snieder, Harold and Spector, Timothy D and Tabara, Yasuharu and Tuomilehto, Jaakko and van Dam, Rob M and Wilson, James G and Wilson, James F and Wolffenbuttel, Bruce H R and Wong, Tien Yin and Wu, Jer-Yuarn and Yuan, Jian-Min and Zonderman, Alan B and Soranzo, Nicole and Guo, Xiuqing and Roberts, David J and Florez, Jose C and Sladek, Robert and Dupuis, Jos{\'e}e and Morris, Andrew P and Tai, E-Shyong and Selvin, Elizabeth and Rotter, Jerome I and Langenberg, Claudia and Barroso, In{\^e}s and Meigs, James B} } @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 {9006, title = {Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus.}, journal = {Nat Commun}, volume = {12}, year = {2021}, month = {2021 12 09}, pages = {7173}, abstract = {

Elevated serum urate levels, a complex trait and major risk factor for incident gout, are~correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6\% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.

}, keywords = {Amino Acid Transport System y+, Cohort Studies, CpG Islands, DNA Methylation, Epigenome, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Transport Proteins, Facilitative, Gout, Humans, Male, Uric Acid}, issn = {2041-1723}, doi = {10.1038/s41467-021-27198-4}, author = {Tin, Adrienne and Schlosser, Pascal and Matias-Garcia, Pamela R and Thio, Chris H L and Joehanes, Roby and Liu, Hongbo and Yu, Zhi and Weihs, Antoine and Hoppmann, Anselm and Grundner-Culemann, Franziska and Min, Josine L and Kuhns, Victoria L Halperin and Adeyemo, Adebowale A and Agyemang, Charles and Arnl{\"o}v, Johan and Aziz, Nasir A and Baccarelli, Andrea and Bochud, Murielle and Brenner, Hermann and Bressler, Jan and Breteler, Monique M B and Carmeli, Cristian and Chaker, Layal and Coresh, Josef and Corre, Tanguy and Correa, Adolfo and Cox, Simon R and Delgado, Graciela E and Eckardt, Kai-Uwe and Ekici, Arif B and Endlich, Karlhans and Floyd, James S and Fraszczyk, Eliza and Gao, Xu and G{\`a}o, Xin and Gelber, Allan C and Ghanbari, Mohsen and Ghasemi, Sahar and Gieger, Christian and Greenland, Philip and Grove, Megan L and Harris, Sarah E and Hemani, Gibran and Henneman, Peter and Herder, Christian and Horvath, Steve and Hou, Lifang and Hurme, Mikko A and Hwang, Shih-Jen and Kardia, Sharon L R and Kasela, Silva and Kleber, Marcus E and Koenig, Wolfgang and Kooner, Jaspal S and Kronenberg, Florian and Kuhnel, Brigitte and Ladd-Acosta, Christine and Lehtim{\"a}ki, Terho and Lind, Lars and Liu, Dan and Lloyd-Jones, Donald M and Lorkowski, Stefan and Lu, Ake T and Marioni, Riccardo E and M{\"a}rz, Winfried and McCartney, Daniel L and Meeks, Karlijn A C and Milani, Lili and Mishra, Pashupati P and Nauck, Matthias and Nowak, Christoph and Peters, Annette and Prokisch, Holger and Psaty, Bruce M and Raitakari, Olli T and Ratliff, Scott M and Reiner, Alex P and Sch{\"o}ttker, Ben and Schwartz, Joel and Sedaghat, Sanaz and Smith, Jennifer A and Sotoodehnia, Nona and Stocker, Hannah R and Stringhini, Silvia and Sundstr{\"o}m, Johan and Swenson, Brenton R and van Meurs, Joyce B J and van Vliet-Ostaptchouk, Jana V and Venema, Andrea and V{\"o}lker, Uwe and Winkelmann, Juliane and Wolffenbuttel, Bruce H R and Zhao, Wei and Zheng, Yinan and Loh, Marie and Snieder, Harold and Waldenberger, Melanie and Levy, Daniel and Akilesh, Shreeram and Woodward, Owen M and Susztak, Katalin and Teumer, Alexander and K{\"o}ttgen, Anna} } @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 {9708, title = {Antithrombin, Protein C, and Protein S: Genome and Transcriptome-Wide Association Studies Identify 7 Novel Loci Regulating Plasma Levels.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {43}, year = {2023}, month = {2023 Jul}, pages = {e254-e269}, abstract = {

BACKGROUND: Antithrombin, PC (protein C), and PS (protein S) are circulating natural anticoagulant proteins that regulate hemostasis and of which partial deficiencies are causes of venous thromboembolism. Previous genetic association studies involving antithrombin, PC, and PS were limited by modest sample sizes or by being restricted to candidate genes. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, we meta-analyzed across ancestries the results from 10 genome-wide association studies of plasma levels of antithrombin, PC, PS free, and PS total.

METHODS: Study participants were of European and African ancestries, and genotype data were imputed to TOPMed, a dense multiancestry reference panel. Each of the 10 studies conducted a genome-wide association studies for each phenotype and summary results were meta-analyzed, stratified by ancestry. Analysis of antithrombin included 25 243 European ancestry and 2688 African ancestry participants, PC analysis included 16 597 European ancestry and 2688 African ancestry participants, PSF and PST analysis included 4113 and 6409 European ancestry participants. We also conducted transcriptome-wide association analyses and multiphenotype analysis to discover additional associations. Novel genome-wide association studies and transcriptome-wide association analyses findings were validated by in vitro functional experiments. Mendelian randomization was performed to assess the causal relationship between these proteins and cardiovascular outcomes.

RESULTS: Genome-wide association studies meta-analyses identified 4 newly associated loci: 3 with antithrombin levels (, , and ) and 1 with PS levels (-). transcriptome-wide association analyses identified 3 newly associated genes: 1 with antithrombin level (), 1 with PC (), and 1 with PS (). In addition, we replicated 7 independent loci reported in previous studies. Functional experiments provided evidence for the involvement of , , and genes in antithrombin regulation.

CONCLUSIONS: The use of larger sample sizes, diverse populations, and a denser imputation reference panel allowed the detection of 7 novel genomic loci associated with plasma antithrombin, PC, and PS levels.

}, keywords = {Anticoagulants, Antithrombin III, Antithrombins, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Protein C, Protein S, Transcriptome}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.122.318213}, author = {Ji, Yuekai and Temprano-Sagrera, Gerard and Holle, Lori A and Bebo, Allison and Brody, Jennifer A and Le, Ngoc-Quynh and Kangro, Kadri and Brown, Michael R and Martinez-Perez, Angel and Sitlani, Colleen M and Suchon, Pierre and Kleber, Marcus E and Emmert, David B and Bilge Ozel, Ayse and Dobson, Dre{\textquoteright}Von A and Tang, Weihong and Llobet, Dolors and Tracy, Russell P and Deleuze, Jean-Francois and Delgado, Graciela E and G{\"o}gele, Martin and Wiggins, Kerri L and Souto, Juan Carlos and Pankow, James S and Taylor, Kent D and Tr{\'e}gou{\"e}t, David-Alexandre and Moissl, Angela P and Fuchsberger, Christian and Rosendaal, Frits R and Morrison, Alanna C and Soria, Jos{\'e} Manuel and Cushman, Mary and Morange, Pierre-Emmanuel and M{\"a}rz, Winfried and Hicks, Andrew A and Desch, Karl C and Johnson, Andrew D and de Vries, Paul S and Wolberg, Alisa S and Smith, Nicholas L and Sabater-Lleal, Maria} } @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} }