@article {1236, title = {Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.}, journal = {Nat Genet}, volume = {42}, year = {2010}, month = {2010 Nov}, pages = {949-60}, abstract = {

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 {\texttimes} 10$^{-}$$^{9}$ to P = 1.8 {\texttimes} 10$^{-}$$^{4}$$^{0}$) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 {\texttimes} 10$^{-}${\textthreesuperior} to P = 1.2 {\texttimes} 10$^{-}${\textonesuperior}{\textthreesuperior}). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

}, keywords = {Adipose Tissue, Age Factors, Chromosome Mapping, Female, Genome, Human, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Sex Characteristics, Waist-Hip Ratio}, issn = {1546-1718}, doi = {10.1038/ng.685}, author = {Heid, Iris M and Jackson, Anne U and Randall, Joshua C and Winkler, Thomas W and Qi, Lu and Steinthorsdottir, Valgerdur and Thorleifsson, Gudmar and Zillikens, M Carola and Speliotes, Elizabeth K and M{\"a}gi, Reedik and Workalemahu, Tsegaselassie and White, Charles C and Bouatia-Naji, Nabila and Harris, Tamara B and Berndt, Sonja I and Ingelsson, Erik and Willer, Cristen J and Weedon, Michael N and Luan, Jian{\textquoteright}an and Vedantam, Sailaja and Esko, T{\~o}nu and Kilpel{\"a}inen, Tuomas O and Kutalik, Zolt{\'a}n and Li, Shengxu and Monda, Keri L and Dixon, Anna L and Holmes, Christopher C and Kaplan, Lee M and Liang, Liming and Min, Josine L and Moffatt, Miriam F and Molony, Cliona and Nicholson, George and Schadt, Eric E and Zondervan, Krina T and Feitosa, Mary F and Ferreira, Teresa and Lango Allen, Hana and Weyant, Robert J and Wheeler, Eleanor and Wood, Andrew R and Estrada, Karol and Goddard, Michael E and Lettre, Guillaume and Mangino, Massimo and Nyholt, Dale R and Purcell, Shaun and Smith, Albert Vernon and Visscher, Peter M and Yang, Jian and McCarroll, Steven A and Nemesh, James and Voight, Benjamin F and Absher, Devin and Amin, Najaf and Aspelund, Thor and Coin, Lachlan and Glazer, Nicole L and Hayward, Caroline and Heard-Costa, Nancy L and Hottenga, Jouke-Jan and Johansson, Asa and Johnson, Toby and Kaakinen, Marika and Kapur, Karen and Ketkar, Shamika and Knowles, Joshua W and Kraft, Peter and Kraja, Aldi T and Lamina, Claudia and Leitzmann, Michael F and McKnight, Barbara and Morris, Andrew P and Ong, Ken K and Perry, John R B and Peters, Marjolein J and Polasek, Ozren and Prokopenko, Inga and Rayner, Nigel W and Ripatti, Samuli and Rivadeneira, Fernando and Robertson, Neil R and Sanna, Serena and Sovio, Ulla and Surakka, Ida and Teumer, Alexander and van Wingerden, Sophie and Vitart, Veronique and Zhao, Jing Hua and Cavalcanti-Proen{\c c}a, Christine and Chines, Peter S and Fisher, Eva and Kulzer, Jennifer R and Lecoeur, C{\'e}cile and Narisu, Narisu and Sandholt, Camilla and Scott, Laura J and Silander, Kaisa and Stark, Klaus and Tammesoo, Mari-Liis and Teslovich, Tanya M and Timpson, Nicholas John and Watanabe, Richard M and Welch, Ryan and Chasman, Daniel I and Cooper, Matthew N and Jansson, John-Olov and Kettunen, Johannes and Lawrence, Robert W and Pellikka, Niina and Perola, Markus and Vandenput, Liesbeth and Alavere, Helene and Almgren, Peter and Atwood, Larry D and Bennett, Amanda J and Biffar, Reiner and Bonnycastle, Lori L and Bornstein, Stefan R and Buchanan, Thomas A and Campbell, Harry and Day, Ian N M and Dei, Mariano and D{\"o}rr, Marcus and Elliott, Paul and Erdos, Michael R and Eriksson, Johan G and Freimer, Nelson B and Fu, Mao and Gaget, Stefan and Geus, Eco J C and Gjesing, Anette P and Grallert, Harald and Gr{\"a}ssler, J{\"u}rgen and Groves, Christopher J and Guiducci, Candace and Hartikainen, Anna-Liisa and Hassanali, Neelam and Havulinna, Aki S and Herzig, Karl-Heinz and Hicks, Andrew A and Hui, Jennie and Igl, Wilmar and Jousilahti, Pekka and Jula, Antti and Kajantie, Eero and Kinnunen, Leena and Kolcic, Ivana and Koskinen, Seppo and Kovacs, Peter and Kroemer, Heyo K and Krzelj, Vjekoslav and Kuusisto, Johanna and Kvaloy, Kirsti and Laitinen, Jaana and Lantieri, Olivier and Lathrop, G Mark and Lokki, Marja-Liisa and Luben, Robert N and Ludwig, Barbara and McArdle, Wendy L and McCarthy, Anne and Morken, Mario A and Nelis, Mari and Neville, Matt J and Par{\'e}, Guillaume and Parker, Alex N and Peden, John F and Pichler, Irene and Pietil{\"a}inen, Kirsi H and Platou, Carl G P and Pouta, Anneli and Ridderstr{\r a}le, Martin and Samani, Nilesh J and Saramies, Jouko and Sinisalo, Juha and Smit, Jan H and Strawbridge, Rona J and Stringham, Heather M and Swift, Amy J and Teder-Laving, Maris and Thomson, Brian and Usala, Gianluca and van Meurs, Joyce B J and van Ommen, Gert-Jan and Vatin, Vincent and Volpato, Claudia B and Wallaschofski, Henri and Walters, G Bragi and Widen, Elisabeth and Wild, Sarah H and Willemsen, Gonneke and Witte, Daniel R and Zgaga, Lina and Zitting, Paavo and Beilby, John P and James, Alan L and K{\"a}h{\"o}nen, Mika and Lehtim{\"a}ki, Terho and Nieminen, Markku S and Ohlsson, Claes and Palmer, Lyle J and Raitakari, Olli and Ridker, Paul M and Stumvoll, Michael and T{\"o}njes, Anke and Viikari, Jorma and Balkau, Beverley and Ben-Shlomo, Yoav and Bergman, Richard N and Boeing, Heiner and Smith, George Davey and Ebrahim, Shah and Froguel, Philippe and Hansen, Torben and Hengstenberg, Christian and Hveem, Kristian and Isomaa, Bo and J{\o}rgensen, Torben and Karpe, Fredrik and Khaw, Kay-Tee and Laakso, Markku and Lawlor, Debbie A and Marre, Michel and Meitinger, Thomas and Metspalu, Andres and Midthjell, Kristian and Pedersen, Oluf and Salomaa, Veikko and Schwarz, Peter E H and Tuomi, Tiinamaija and Tuomilehto, Jaakko and Valle, Timo T and Wareham, Nicholas J and Arnold, Alice M and Beckmann, Jacques S and Bergmann, Sven and Boerwinkle, Eric and Boomsma, Dorret I and Caulfield, Mark J and Collins, Francis S and Eiriksdottir, Gudny and Gudnason, Vilmundur and Gyllensten, Ulf and Hamsten, Anders and Hattersley, Andrew T and Hofman, Albert and Hu, Frank B and Illig, Thomas and Iribarren, Carlos and Jarvelin, Marjo-Riitta and Kao, W H Linda and Kaprio, Jaakko and Launer, Lenore J and Munroe, Patricia B and Oostra, Ben and Penninx, Brenda W and Pramstaller, Peter P and Psaty, Bruce M and Quertermous, Thomas and Rissanen, Aila and Rudan, Igor and Shuldiner, Alan R and Soranzo, Nicole and Spector, Timothy D and Syv{\"a}nen, Ann-Christine and Uda, Manuela and Uitterlinden, Andre and V{\"o}lzke, Henry and Vollenweider, Peter and Wilson, James F and Witteman, Jacqueline C and Wright, Alan F and Abecasis, Goncalo R and Boehnke, Michael and Borecki, Ingrid B and Deloukas, Panos and Frayling, Timothy M and Groop, Leif C and Haritunians, Talin and Hunter, David J and Kaplan, Robert C and North, Kari E and O{\textquoteright}Connell, Jeffrey R and Peltonen, Leena and Schlessinger, David and Strachan, David P and Hirschhorn, Joel N and Assimes, Themistocles L and Wichmann, H-Erich and Thorsteinsdottir, Unnur and van Duijn, Cornelia M and Stefansson, Kari and Cupples, L Adrienne and Loos, Ruth J F and Barroso, In{\^e}s and McCarthy, Mark I and Fox, Caroline S and Mohlke, Karen L and Lindgren, Cecilia M} } @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 {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} }