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  • 1
    Publication Date: 2010-10-01
    Description: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P 〈 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955183/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955183/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lango Allen, Hana -- Estrada, Karol -- Lettre, Guillaume -- Berndt, Sonja I -- Weedon, Michael N -- Rivadeneira, Fernando -- Willer, Cristen J -- Jackson, Anne U -- Vedantam, Sailaja -- Raychaudhuri, Soumya -- Ferreira, Teresa -- Wood, Andrew R -- Weyant, Robert J -- Segre, Ayellet V -- Speliotes, Elizabeth K -- Wheeler, Eleanor -- Soranzo, Nicole -- Park, Ju-Hyun -- Yang, Jian -- Gudbjartsson, Daniel -- Heard-Costa, Nancy L -- Randall, Joshua C -- Qi, Lu -- Vernon Smith, Albert -- Magi, Reedik -- Pastinen, Tomi -- Liang, Liming -- Heid, Iris M -- Luan, Jian'an -- Thorleifsson, Gudmar -- Winkler, Thomas W -- Goddard, Michael E -- Sin Lo, Ken -- Palmer, Cameron -- Workalemahu, Tsegaselassie -- Aulchenko, Yurii S -- Johansson, Asa -- Zillikens, M Carola -- Feitosa, Mary F -- Esko, Tonu -- Johnson, Toby -- Ketkar, Shamika -- Kraft, Peter -- Mangino, Massimo -- Prokopenko, Inga -- Absher, Devin -- Albrecht, Eva -- Ernst, Florian -- Glazer, Nicole L -- Hayward, Caroline -- Hottenga, Jouke-Jan -- Jacobs, Kevin B -- Knowles, Joshua W -- Kutalik, Zoltan -- Monda, Keri L -- Polasek, Ozren -- Preuss, Michael -- Rayner, Nigel W -- Robertson, Neil R -- Steinthorsdottir, Valgerdur -- Tyrer, Jonathan P -- Voight, Benjamin F -- Wiklund, Fredrik -- Xu, Jianfeng -- Zhao, Jing Hua -- Nyholt, Dale R -- Pellikka, Niina -- Perola, Markus -- Perry, John R B -- Surakka, Ida -- Tammesoo, Mari-Liis -- Altmaier, Elizabeth L -- Amin, Najaf -- Aspelund, Thor -- Bhangale, Tushar -- Boucher, Gabrielle -- Chasman, Daniel I -- Chen, Constance -- Coin, Lachlan -- Cooper, Matthew N -- Dixon, Anna L -- Gibson, Quince -- Grundberg, Elin -- Hao, Ke -- Juhani Junttila, M -- Kaplan, Lee M -- Kettunen, Johannes -- Konig, Inke R -- Kwan, Tony -- Lawrence, Robert W -- Levinson, Douglas F -- Lorentzon, Mattias -- McKnight, Barbara -- Morris, Andrew P -- Muller, Martina -- Suh Ngwa, Julius -- Purcell, Shaun -- Rafelt, Suzanne -- Salem, Rany M -- Salvi, Erika -- Sanna, Serena -- Shi, Jianxin -- Sovio, Ulla -- Thompson, John R -- Turchin, Michael C -- Vandenput, Liesbeth -- Verlaan, Dominique J -- Vitart, Veronique -- White, Charles C -- Ziegler, Andreas -- Almgren, Peter -- Balmforth, Anthony J -- Campbell, Harry -- Citterio, Lorena -- De Grandi, Alessandro -- Dominiczak, Anna -- Duan, Jubao -- Elliott, Paul -- Elosua, Roberto -- Eriksson, Johan G -- Freimer, Nelson B -- Geus, Eco J C -- Glorioso, Nicola -- Haiqing, Shen -- Hartikainen, Anna-Liisa -- Havulinna, Aki S -- Hicks, Andrew A -- Hui, Jennie -- Igl, Wilmar -- Illig, Thomas -- Jula, Antti -- Kajantie, Eero -- Kilpelainen, Tuomas O -- Koiranen, Markku -- Kolcic, Ivana -- Koskinen, Seppo -- Kovacs, Peter -- Laitinen, Jaana -- Liu, Jianjun -- Lokki, Marja-Liisa -- Marusic, Ana -- Maschio, Andrea -- Meitinger, Thomas -- Mulas, Antonella -- Pare, Guillaume -- Parker, Alex N -- Peden, John F -- Petersmann, Astrid -- Pichler, Irene -- Pietilainen, Kirsi H -- Pouta, Anneli -- Ridderstrale, Martin -- Rotter, Jerome I -- Sambrook, Jennifer G -- Sanders, Alan R -- Schmidt, Carsten Oliver -- Sinisalo, Juha -- Smit, Jan H -- Stringham, Heather M -- Bragi Walters, G -- Widen, Elisabeth -- Wild, Sarah H -- Willemsen, Gonneke -- Zagato, Laura -- Zgaga, Lina -- Zitting, Paavo -- Alavere, Helene -- Farrall, Martin -- McArdle, Wendy L -- Nelis, Mari -- Peters, Marjolein J -- Ripatti, Samuli -- van Meurs, Joyce B J -- Aben, Katja K -- Ardlie, Kristin G -- Beckmann, Jacques S -- Beilby, John P -- Bergman, Richard N -- Bergmann, Sven -- Collins, Francis S -- Cusi, Daniele -- den Heijer, Martin -- Eiriksdottir, Gudny -- Gejman, Pablo V -- Hall, Alistair S -- Hamsten, Anders -- Huikuri, Heikki V -- Iribarren, Carlos -- Kahonen, Mika -- Kaprio, Jaakko -- Kathiresan, Sekar -- Kiemeney, Lambertus -- Kocher, Thomas -- Launer, Lenore J -- Lehtimaki, Terho -- Melander, Olle -- Mosley, Tom H Jr -- Musk, Arthur W -- Nieminen, Markku S -- O'Donnell, Christopher J -- Ohlsson, Claes -- Oostra, Ben -- Palmer, Lyle J -- Raitakari, Olli -- Ridker, Paul M -- Rioux, John D -- Rissanen, Aila -- Rivolta, Carlo -- Schunkert, Heribert -- Shuldiner, Alan R -- Siscovick, David S -- Stumvoll, Michael -- Tonjes, Anke -- Tuomilehto, Jaakko -- van Ommen, Gert-Jan -- Viikari, Jorma -- Heath, Andrew C -- Martin, Nicholas G -- Montgomery, Grant W -- Province, Michael A -- Kayser, Manfred -- Arnold, Alice M -- Atwood, Larry D -- Boerwinkle, Eric -- Chanock, Stephen J -- Deloukas, Panos -- Gieger, Christian -- Gronberg, Henrik -- Hall, Per -- Hattersley, Andrew T -- Hengstenberg, Christian -- Hoffman, Wolfgang -- Lathrop, G Mark -- Salomaa, Veikko -- Schreiber, Stefan -- Uda, Manuela -- Waterworth, Dawn -- Wright, Alan F -- Assimes, Themistocles L -- Barroso, Ines -- Hofman, Albert -- Mohlke, Karen L -- Boomsma, Dorret I -- Caulfield, Mark J -- Cupples, L Adrienne -- Erdmann, Jeanette -- Fox, Caroline S -- Gudnason, Vilmundur -- Gyllensten, Ulf -- Harris, Tamara B -- Hayes, Richard B -- Jarvelin, Marjo-Riitta -- Mooser, Vincent -- Munroe, Patricia B -- Ouwehand, Willem H -- Penninx, Brenda W -- Pramstaller, Peter P -- Quertermous, Thomas -- Rudan, Igor -- Samani, Nilesh J -- Spector, Timothy D -- Volzke, Henry -- Watkins, Hugh -- Wilson, James F -- Groop, Leif C -- Haritunians, Talin -- Hu, Frank B -- Kaplan, Robert C -- Metspalu, Andres -- North, Kari E -- Schlessinger, David -- Wareham, Nicholas J -- Hunter, David J -- O'Connell, Jeffrey R -- Strachan, David P -- Wichmann, H-Erich -- Borecki, Ingrid B -- van Duijn, Cornelia M -- Schadt, Eric E -- Thorsteinsdottir, Unnur -- Peltonen, Leena -- Uitterlinden, Andre G -- Visscher, Peter M -- Chatterjee, Nilanjan -- Loos, Ruth J F -- Boehnke, Michael -- McCarthy, Mark I -- Ingelsson, Erik -- Lindgren, Cecilia M -- Abecasis, Goncalo R -- Stefansson, Kari -- Frayling, Timothy M -- Hirschhorn, Joel N -- 064890/Wellcome Trust/United Kingdom -- 068545/Wellcome Trust/United Kingdom -- 068545/Z/02/Wellcome Trust/United Kingdom -- 072856/Wellcome Trust/United Kingdom -- 072960/Wellcome Trust/United Kingdom -- 075491/Wellcome Trust/United Kingdom -- 076113/Wellcome Trust/United Kingdom -- 076113/B/04/Z/Wellcome Trust/United Kingdom -- 076113/C/04/Z/Wellcome Trust/United Kingdom -- 077016/Wellcome Trust/United Kingdom -- 077016/Z/05/Z/Wellcome Trust/United Kingdom -- 079557/Wellcome Trust/United Kingdom -- 079771/Wellcome Trust/United Kingdom -- 079895/Wellcome Trust/United Kingdom -- 081682/Wellcome Trust/United Kingdom -- 081682/Z/06/Z/Wellcome Trust/United Kingdom -- 083270/Wellcome Trust/United Kingdom -- 084183/Z/07/Z/Wellcome Trust/United Kingdom -- 085301/Wellcome Trust/United Kingdom -- 085301/Z/08/Z/Wellcome Trust/United Kingdom -- 086596/Wellcome Trust/United Kingdom -- 086596/Z/08/Z/Wellcome Trust/United Kingdom -- 088885/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 091746/Wellcome Trust/United Kingdom -- 091746/Z/10/Z/Wellcome Trust/United Kingdom -- 263-MA-410953/PHS HHS/ -- AA014041/AA/NIAAA NIH HHS/ -- AA07535/AA/NIAAA NIH HHS/ -- AA10248/AA/NIAAA NIH HHS/ -- AA13320/AA/NIAAA NIH HHS/ -- AA13321/AA/NIAAA NIH HHS/ -- AA13326/AA/NIAAA NIH HHS/ -- CA047988/CA/NCI NIH HHS/ -- CA49449/CA/NCI NIH HHS/ -- CA50385/CA/NCI NIH HHS/ -- CA65725/CA/NCI NIH HHS/ -- CA67262/CA/NCI NIH HHS/ -- CA87969/CA/NCI NIH HHS/ -- CZB/4/276/Chief Scientist Office/United Kingdom -- 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R01-HL088119/HL/NHLBI NIH HHS/ -- R01-HL59367/HL/NHLBI NIH HHS/ -- R01-MH059160/MH/NIMH NIH HHS/ -- R01-MH59565/MH/NIMH NIH HHS/ -- R01-MH59566/MH/NIMH NIH HHS/ -- R01-MH59571/MH/NIMH NIH HHS/ -- R01-MH59586/MH/NIMH NIH HHS/ -- R01-MH59587/MH/NIMH NIH HHS/ -- R01-MH59588/MH/NIMH NIH HHS/ -- R01-MH60870/MH/NIMH NIH HHS/ -- R01-MH60879/MH/NIMH NIH HHS/ -- R01-MH61675/MH/NIMH NIH HHS/ -- R01-MH63706/MH/NIMH NIH HHS/ -- R01-MH67257/MH/NIMH NIH HHS/ -- R01-MH79469/MH/NIMH NIH HHS/ -- R01-MH81800/MH/NIMH NIH HHS/ -- RC2 HG005581/HG/NHGRI NIH HHS/ -- RC2 HG005581-02/HG/NHGRI NIH HHS/ -- RL1 MH083268/MH/NIMH NIH HHS/ -- RL1 MH083268-05/MH/NIMH NIH HHS/ -- RL1-MH083268/MH/NIMH NIH HHS/ -- T32-HG00040/HG/NHGRI NIH HHS/ -- U01 CA049449/CA/NCI NIH HHS/ -- U01 CA049449-21/CA/NCI NIH HHS/ -- U01 CA098233/CA/NCI NIH HHS/ -- U01 CA098233-08/CA/NCI NIH HHS/ -- U01 DK062370/DK/NIDDK NIH HHS/ -- U01 DK062370-08/DK/NIDDK NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 GM074518/GM/NIGMS NIH HHS/ -- U01 GM074518-05/GM/NIGMS NIH HHS/ -- U01 HG004399/HG/NHGRI NIH HHS/ -- U01 HG004399-02/HG/NHGRI NIH HHS/ -- U01 HG004402/HG/NHGRI NIH HHS/ -- U01 HG004402-02/HG/NHGRI NIH HHS/ -- U01 HG005214/HG/NHGRI NIH HHS/ -- U01 HG005214-02/HG/NHGRI NIH HHS/ -- U01 HL069757/HL/NHLBI NIH HHS/ -- U01 HL069757-10/HL/NHLBI NIH HHS/ -- U01 HL072515/HL/NHLBI NIH HHS/ -- U01 HL072515-06/HL/NHLBI NIH HHS/ -- U01 HL080295/HL/NHLBI NIH HHS/ -- U01 HL080295-04/HL/NHLBI NIH HHS/ -- U01 HL084729/HL/NHLBI NIH HHS/ -- U01 HL084729-03/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U01 HL084756-03/HL/NHLBI NIH HHS/ -- U01 MH079469/MH/NIMH NIH HHS/ -- U01 MH079469-03/MH/NIMH NIH HHS/ -- U01 MH079470/MH/NIMH NIH HHS/ -- U01 MH079470-03/MH/NIMH NIH HHS/ -- U01-CA098233/CA/NCI NIH HHS/ -- U01-GM074518/GM/NIGMS NIH HHS/ -- U01-HG004399/HG/NHGRI NIH HHS/ -- U01-HG004402/HG/NHGRI NIH HHS/ -- U01-HL080295/HL/NHLBI NIH HHS/ -- U01-HL084756/HL/NHLBI NIH HHS/ -- U01-HL72515/HL/NHLBI NIH HHS/ -- U01-MH79469/MH/NIMH NIH HHS/ -- U01-MH79470/MH/NIMH NIH HHS/ -- U54-RR020278/RR/NCRR NIH HHS/ -- UL1-RR025005/RR/NCRR NIH HHS/ -- Z01-AG00675/AG/NIA NIH HHS/ -- Z01-AG007380/AG/NIA NIH HHS/ -- Z01-HG000024/HG/NHGRI NIH HHS/ -- Cancer Research UK/United Kingdom -- Intramural NIH HHS/ -- England -- Nature. 2010 Oct 14;467(7317):832-8. doi: 10.1038/nature09410. Epub 2010 Sep 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881960" target="_blank"〉PubMed〈/a〉
    Keywords: Body Height/*genetics ; Chromosomes, Human, Pair 3/genetics ; Genetic Loci/*genetics ; Genetic Predisposition to Disease/genetics ; Genome, Human/*genetics ; Genome-Wide Association Study ; Humans ; Metabolic Networks and Pathways/*genetics ; Multifactorial Inheritance/genetics ; Phenotype ; Polymorphism, Single Nucleotide/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2011-09-02
    Description: Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) 〈/= 18.5 kg per m(2) in adults and 〈/= -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a approximately 600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637175/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637175/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jacquemont, Sebastien -- Reymond, Alexandre -- Zufferey, Flore -- Harewood, Louise -- Walters, Robin G -- Kutalik, Zoltan -- Martinet, Danielle -- Shen, Yiping -- Valsesia, Armand -- Beckmann, Noam D -- Thorleifsson, Gudmar -- Belfiore, Marco -- Bouquillon, Sonia -- Campion, Dominique -- de Leeuw, Nicole -- de Vries, Bert B A -- Esko, Tonu -- Fernandez, Bridget A -- Fernandez-Aranda, Fernando -- Fernandez-Real, Jose Manuel -- Gratacos, Monica -- Guilmatre, Audrey -- Hoyer, Juliane -- Jarvelin, Marjo-Riitta -- Kooy, R Frank -- Kurg, Ants -- Le Caignec, Cedric -- Mannik, Katrin -- Platt, Orah S -- Sanlaville, Damien -- Van Haelst, Mieke M -- Villatoro Gomez, Sergi -- Walha, Faida -- Wu, Bai-Lin -- Yu, Yongguo -- Aboura, Azzedine -- Addor, Marie-Claude -- Alembik, Yves -- Antonarakis, Stylianos E -- Arveiler, Benoit -- Barth, Magalie -- Bednarek, Nathalie -- Bena, Frederique -- Bergmann, Sven -- Beri, Mylene -- Bernardini, Laura -- Blaumeiser, Bettina -- Bonneau, Dominique -- Bottani, Armand -- Boute, Odile -- Brunner, Han G -- Cailley, Dorothee -- Callier, Patrick -- Chiesa, Jean -- Chrast, Jacqueline -- Coin, Lachlan -- Coutton, Charles -- Cuisset, Jean-Marie -- Cuvellier, Jean-Christophe -- David, Albert -- de Freminville, Benedicte -- Delobel, Bruno -- Delrue, Marie-Ange -- Demeer, Benedicte -- Descamps, Dominique -- Didelot, Gerard -- Dieterich, Klaus -- Disciglio, Vittoria -- Doco-Fenzy, Martine -- Drunat, Severine -- Duban-Bedu, Benedicte -- Dubourg, Christele -- El-Sayed Moustafa, Julia S -- Elliott, Paul -- Faas, Brigitte H W -- Faivre, Laurence -- Faudet, Anne -- Fellmann, Florence -- Ferrarini, Alessandra -- Fisher, Richard -- Flori, Elisabeth -- Forer, Lukas -- Gaillard, Dominique -- Gerard, Marion -- Gieger, Christian -- Gimelli, Stefania -- Gimelli, Giorgio -- Grabe, Hans J -- Guichet, Agnes -- Guillin, Olivier -- Hartikainen, Anna-Liisa -- Heron, Delphine -- Hippolyte, Loyse -- Holder, Muriel -- Homuth, Georg -- Isidor, Bertrand -- Jaillard, Sylvie -- Jaros, Zdenek -- Jimenez-Murcia, Susana -- Helas, Geraldine Joly -- Jonveaux, Philippe -- Kaksonen, Satu -- Keren, Boris -- Kloss-Brandstatter, Anita -- Knoers, Nine V A M -- Koolen, David A -- Kroisel, Peter M -- Kronenberg, Florian -- Labalme, Audrey -- Landais, Emilie -- Lapi, Elisabetta -- Layet, Valerie -- Legallic, Solenn -- Leheup, Bruno -- Leube, Barbara -- Lewis, Suzanne -- Lucas, Josette -- MacDermot, Kay D -- Magnusson, Pall -- Marshall, Christian -- Mathieu-Dramard, Michele -- McCarthy, Mark I -- Meitinger, Thomas -- Mencarelli, Maria Antonietta -- Merla, Giuseppe -- Moerman, Alexandre -- Mooser, Vincent -- Morice-Picard, Fanny -- Mucciolo, Mafalda -- Nauck, Matthias -- Ndiaye, Ndeye Coumba -- Nordgren, Ann -- Pasquier, Laurent -- Petit, Florence -- Pfundt, Rolph -- Plessis, Ghislaine -- Rajcan-Separovic, Evica -- Ramelli, Gian Paolo -- Rauch, Anita -- Ravazzolo, Roberto -- Reis, Andre -- Renieri, Alessandra -- Richart, Cristobal -- Ried, Janina S -- Rieubland, Claudine -- Roberts, Wendy -- Roetzer, Katharina M -- Rooryck, Caroline -- Rossi, Massimiliano -- Saemundsen, Evald -- Satre, Veronique -- Schurmann, Claudia -- Sigurdsson, Engilbert -- Stavropoulos, Dimitri J -- Stefansson, Hreinn -- Tengstrom, Carola -- Thorsteinsdottir, Unnur -- Tinahones, Francisco J -- Touraine, Renaud -- Vallee, Louis -- van Binsbergen, Ellen -- Van der Aa, Nathalie -- Vincent-Delorme, Catherine -- Visvikis-Siest, Sophie -- Vollenweider, Peter -- Volzke, Henry -- Vulto-van Silfhout, Anneke T -- Waeber, Gerard -- Wallgren-Pettersson, Carina -- Witwicki, Robert M -- Zwolinksi, Simon -- Andrieux, Joris -- Estivill, Xavier -- Gusella, James F -- Gustafsson, Omar -- Metspalu, Andres -- Scherer, Stephen W -- Stefansson, Kari -- Blakemore, Alexandra I F -- Beckmann, Jacques S -- Froguel, Philippe -- 090532/Wellcome Trust/United Kingdom -- 1RL1MH083268-01/MH/NIMH NIH HHS/ -- 5R01HL087679-02/HL/NHLBI NIH HHS/ -- 5R01MH63706:02/MH/NIMH NIH HHS/ -- AS2173/Autism Speaks/ -- G0500539/Medical Research Council/United Kingdom -- G0600705/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- GM061354/GM/NIGMS NIH HHS/ -- MH071425/MH/NIMH NIH HHS/ -- MOP 74502/Canadian Institutes of Health Research/Canada -- Wellcome Trust/United Kingdom -- England -- Nature. 2011 Aug 31;478(7367):97-102. doi: 10.1038/nature10406.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21881559" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Aging ; Body Height/genetics ; *Body Mass Index ; Case-Control Studies ; Child ; Child, Preschool ; Chromosomes, Human, Pair 16/*genetics ; Cohort Studies ; Comparative Genomic Hybridization ; Developmental Disabilities/genetics ; Energy Metabolism/genetics ; Europe ; Female ; Gene Dosage/*genetics ; Gene Duplication/genetics ; Gene Expression Profiling ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Head/anatomy & histology ; Heterozygote ; Humans ; Infant ; Infant, Newborn ; Male ; Mental Disorders/genetics ; Middle Aged ; Mutation/genetics ; North America ; Obesity/*genetics ; *Phenotype ; RNA, Messenger/analysis/genetics ; Sequence Deletion/genetics ; Thinness/*genetics ; Transcription, Genetic ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-02-13
    Description: Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 〈 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for approximately 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for 〉20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382211/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382211/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Locke, Adam E -- Kahali, Bratati -- Berndt, Sonja I -- Justice, Anne E -- Pers, Tune H -- Day, Felix R -- Powell, Corey -- Vedantam, Sailaja -- Buchkovich, Martin L -- Yang, Jian -- Croteau-Chonka, Damien C -- Esko, Tonu -- Fall, Tove -- Ferreira, Teresa -- Gustafsson, Stefan -- Kutalik, Zoltan -- Luan, Jian'an -- Magi, Reedik -- Randall, Joshua C -- Winkler, Thomas W -- Wood, Andrew R -- Workalemahu, Tsegaselassie -- Faul, Jessica D -- Smith, Jennifer A -- Hua Zhao, Jing -- Zhao, Wei -- Chen, Jin -- Fehrmann, Rudolf -- Hedman, Asa K -- Karjalainen, Juha -- Schmidt, Ellen M -- Absher, Devin -- Amin, Najaf -- Anderson, Denise -- Beekman, Marian -- Bolton, Jennifer L -- Bragg-Gresham, Jennifer L -- Buyske, Steven -- Demirkan, Ayse -- Deng, Guohong -- Ehret, Georg B -- Feenstra, Bjarke -- Feitosa, Mary F -- Fischer, Krista -- Goel, Anuj -- Gong, Jian -- Jackson, Anne U -- Kanoni, Stavroula -- Kleber, Marcus E -- Kristiansson, Kati -- Lim, Unhee -- Lotay, Vaneet -- Mangino, Massimo -- Mateo Leach, Irene -- Medina-Gomez, Carolina -- Medland, Sarah E -- Nalls, Michael A -- Palmer, Cameron D -- Pasko, Dorota -- Pechlivanis, Sonali -- Peters, Marjolein J -- Prokopenko, Inga -- Shungin, Dmitry -- Stancakova, Alena -- Strawbridge, Rona J -- Ju Sung, Yun -- Tanaka, Toshiko -- Teumer, Alexander -- Trompet, Stella -- van der Laan, Sander W -- van Setten, Jessica -- Van Vliet-Ostaptchouk, Jana V -- Wang, Zhaoming -- Yengo, Loic -- Zhang, Weihua -- Isaacs, Aaron -- Albrecht, Eva -- Arnlov, Johan -- Arscott, Gillian M -- Attwood, Antony P -- Bandinelli, Stefania -- Barrett, Amy -- Bas, Isabelita N -- Bellis, Claire -- Bennett, Amanda J -- Berne, Christian -- Blagieva, Roza -- Bluher, Matthias -- Bohringer, Stefan -- Bonnycastle, Lori L -- Bottcher, Yvonne -- Boyd, Heather A -- Bruinenberg, Marcel -- Caspersen, Ida H -- Ida Chen, Yii-Der -- Clarke, Robert -- Daw, E Warwick -- de Craen, Anton J M -- Delgado, Graciela -- Dimitriou, Maria -- Doney, Alex S F -- Eklund, Niina -- Estrada, Karol -- Eury, Elodie -- Folkersen, Lasse -- Fraser, Ross M -- Garcia, Melissa E -- Geller, Frank -- Giedraitis, Vilmantas -- Gigante, Bruna -- Go, Alan S -- Golay, Alain -- Goodall, Alison H -- Gordon, Scott D -- Gorski, Mathias -- Grabe, Hans-Jorgen -- Grallert, Harald -- Grammer, Tanja B -- Grassler, Jurgen -- Gronberg, Henrik -- Groves, Christopher J -- Gusto, Gaelle -- Haessler, Jeffrey -- Hall, Per -- Haller, Toomas -- Hallmans, Goran -- Hartman, Catharina A -- Hassinen, Maija -- Hayward, Caroline -- Heard-Costa, Nancy L -- Helmer, Quinta -- Hengstenberg, Christian -- Holmen, Oddgeir -- Hottenga, Jouke-Jan -- James, Alan L -- Jeff, Janina M -- Johansson, Asa -- Jolley, Jennifer -- Juliusdottir, Thorhildur -- Kinnunen, Leena -- Koenig, Wolfgang -- Koskenvuo, Markku -- Kratzer, Wolfgang -- Laitinen, Jaana -- Lamina, Claudia -- Leander, Karin -- Lee, Nanette R -- Lichtner, Peter -- Lind, Lars -- Lindstrom, Jaana -- Sin Lo, Ken -- Lobbens, Stephane -- Lorbeer, Roberto -- Lu, Yingchang -- Mach, Francois -- Magnusson, Patrik K E -- Mahajan, Anubha -- McArdle, Wendy L -- McLachlan, Stela -- Menni, Cristina -- Merger, Sigrun -- Mihailov, Evelin -- Milani, Lili -- Moayyeri, Alireza -- Monda, Keri L -- Morken, Mario A -- Mulas, Antonella -- Muller, Gabriele -- Muller-Nurasyid, Martina -- Musk, Arthur W -- Nagaraja, Ramaiah -- Nothen, Markus M -- Nolte, Ilja M -- Pilz, Stefan -- Rayner, Nigel W -- Renstrom, Frida -- Rettig, Rainer -- Ried, Janina S -- Ripke, Stephan -- Robertson, Neil R -- Rose, Lynda M -- Sanna, Serena -- Scharnagl, Hubert -- Scholtens, Salome -- Schumacher, Fredrick R -- Scott, William R -- Seufferlein, Thomas -- Shi, Jianxin -- Vernon Smith, Albert -- Smolonska, Joanna -- Stanton, Alice V -- Steinthorsdottir, Valgerdur -- Stirrups, Kathleen -- Stringham, Heather M -- Sundstrom, Johan -- Swertz, Morris A -- Swift, Amy J -- Syvanen, Ann-Christine -- Tan, Sian-Tsung -- Tayo, Bamidele O -- Thorand, Barbara -- Thorleifsson, Gudmar -- Tyrer, Jonathan P -- Uh, Hae-Won -- Vandenput, Liesbeth -- Verhulst, Frank C -- Vermeulen, Sita H -- Verweij, Niek -- Vonk, Judith M -- Waite, Lindsay L -- Warren, Helen R -- Waterworth, Dawn -- Weedon, Michael N -- Wilkens, Lynne R -- Willenborg, Christina -- Wilsgaard, Tom -- Wojczynski, Mary K -- Wong, Andrew -- Wright, Alan F -- Zhang, Qunyuan -- LifeLines Cohort Study -- Brennan, Eoin P -- Choi, Murim -- Dastani, Zari -- Drong, Alexander W -- Eriksson, Per -- Franco-Cereceda, Anders -- Gadin, Jesper R -- Gharavi, Ali G -- Goddard, Michael E -- Handsaker, Robert E -- Huang, Jinyan -- Karpe, Fredrik -- Kathiresan, Sekar -- Keildson, Sarah -- Kiryluk, Krzysztof -- Kubo, Michiaki -- Lee, Jong-Young -- Liang, Liming -- Lifton, Richard P -- Ma, Baoshan -- McCarroll, Steven A -- McKnight, Amy J -- Min, Josine L -- Moffatt, Miriam F -- Montgomery, Grant W -- Murabito, Joanne M -- Nicholson, George -- Nyholt, Dale R -- Okada, Yukinori -- Perry, John R B -- Dorajoo, Rajkumar -- Reinmaa, Eva -- Salem, Rany M -- Sandholm, Niina -- Scott, Robert A -- Stolk, Lisette -- Takahashi, Atsushi -- Tanaka, Toshihiro -- Van't Hooft, Ferdinand M -- Vinkhuyzen, Anna A E -- Westra, Harm-Jan -- Zheng, Wei -- Zondervan, Krina T -- ADIPOGen Consortium -- AGEN-BMI Working Group -- CARDIOGRAMplusC4D Consortium -- CKDGen Consortium -- GLGC -- ICBP -- MAGIC Investigators -- MuTHER Consortium -- MIGen Consortium -- PAGE Consortium -- ReproGen Consortium -- GENIE Consortium -- International Endogene Consortium -- Heath, Andrew C -- Arveiler, Dominique -- Bakker, Stephan J L -- Beilby, John -- Bergman, Richard N -- Blangero, John -- Bovet, Pascal -- Campbell, Harry -- Caulfield, Mark J -- Cesana, Giancarlo -- Chakravarti, Aravinda -- Chasman, Daniel I -- Chines, Peter S -- Collins, Francis S -- Crawford, Dana C -- Cupples, L Adrienne -- Cusi, Daniele -- Danesh, John -- de Faire, Ulf -- den Ruijter, Hester M -- Dominiczak, Anna F -- Erbel, Raimund -- Erdmann, Jeanette -- Eriksson, Johan G -- Farrall, Martin -- Felix, Stephan B -- Ferrannini, Ele -- Ferrieres, Jean -- Ford, Ian -- Forouhi, Nita G -- Forrester, Terrence -- Franco, Oscar H -- Gansevoort, Ron T -- Gejman, Pablo V -- Gieger, Christian -- Gottesman, Omri -- Gudnason, Vilmundur -- Gyllensten, Ulf -- Hall, Alistair S -- Harris, Tamara B -- Hattersley, Andrew T -- Hicks, Andrew A -- Hindorff, Lucia A -- Hingorani, Aroon D -- Hofman, Albert -- Homuth, Georg -- Hovingh, G Kees -- Humphries, Steve E -- Hunt, Steven C -- Hypponen, Elina -- Illig, Thomas -- Jacobs, Kevin B -- Jarvelin, Marjo-Riitta -- Jockel, Karl-Heinz -- Johansen, Berit -- Jousilahti, Pekka -- Jukema, J Wouter -- Jula, Antti M -- Kaprio, Jaakko -- Kastelein, John J P -- Keinanen-Kiukaanniemi, Sirkka M -- Kiemeney, Lambertus A -- Knekt, Paul -- Kooner, Jaspal S -- Kooperberg, Charles -- Kovacs, Peter -- Kraja, Aldi T -- Kumari, Meena -- Kuusisto, Johanna -- Lakka, Timo A -- Langenberg, Claudia -- Le Marchand, Loic -- Lehtimaki, Terho -- Lyssenko, Valeriya -- Mannisto, Satu -- Marette, Andre -- Matise, Tara C -- McKenzie, Colin A -- McKnight, Barbara -- Moll, Frans L -- Morris, Andrew D -- Morris, Andrew P -- Murray, Jeffrey C -- Nelis, Mari -- Ohlsson, Claes -- Oldehinkel, Albertine J -- Ong, Ken K -- Madden, Pamela A F -- Pasterkamp, Gerard -- Peden, John F -- Peters, Annette -- Postma, Dirkje S -- Pramstaller, Peter P -- Price, Jackie F -- Qi, Lu -- Raitakari, Olli T -- Rankinen, Tuomo -- Rao, D C -- Rice, Treva K -- Ridker, Paul M -- Rioux, John D -- Ritchie, Marylyn D -- Rudan, Igor -- Salomaa, Veikko -- Samani, Nilesh J -- Saramies, Jouko -- Sarzynski, Mark A -- Schunkert, Heribert -- Schwarz, Peter E H -- Sever, Peter -- Shuldiner, Alan R -- Sinisalo, Juha -- Stolk, Ronald P -- Strauch, Konstantin -- Tonjes, Anke -- Tregouet, David-Alexandre -- Tremblay, Angelo -- Tremoli, Elena -- Virtamo, Jarmo -- Vohl, Marie-Claude -- Volker, Uwe -- Waeber, Gerard -- Willemsen, Gonneke -- Witteman, Jacqueline C -- Zillikens, M Carola -- Adair, Linda S -- Amouyel, Philippe -- Asselbergs, Folkert W -- Assimes, Themistocles L -- Bochud, Murielle -- Boehm, Bernhard O -- Boerwinkle, Eric -- Bornstein, Stefan R -- Bottinger, Erwin P -- Bouchard, Claude -- Cauchi, Stephane -- Chambers, John C -- Chanock, Stephen J -- Cooper, Richard S -- de Bakker, Paul I W -- Dedoussis, George -- Ferrucci, Luigi -- Franks, Paul W -- Froguel, Philippe -- Groop, Leif C -- Haiman, Christopher A -- Hamsten, Anders -- Hui, Jennie -- Hunter, David J -- Hveem, Kristian -- Kaplan, Robert C -- Kivimaki, Mika -- Kuh, Diana -- Laakso, Markku -- Liu, Yongmei -- Martin, Nicholas G -- Marz, Winfried -- Melbye, Mads -- Metspalu, Andres -- Moebus, Susanne -- Munroe, Patricia B -- Njolstad, Inger -- Oostra, Ben A -- Palmer, Colin N A -- Pedersen, Nancy L -- Perola, Markus -- Perusse, Louis -- Peters, Ulrike -- Power, Chris -- Quertermous, Thomas -- Rauramaa, Rainer -- Rivadeneira, Fernando -- Saaristo, Timo E -- Saleheen, Danish -- Sattar, Naveed -- Schadt, Eric E -- Schlessinger, David -- Slagboom, P Eline -- Snieder, Harold -- Spector, Tim D -- Thorsteinsdottir, Unnur -- Stumvoll, Michael -- Tuomilehto, Jaakko -- Uitterlinden, Andre G -- Uusitupa, Matti -- van der Harst, Pim -- Walker, Mark -- Wallaschofski, Henri -- Wareham, Nicholas J -- Watkins, Hugh -- Weir, David R -- Wichmann, H-Erich -- Wilson, James F -- Zanen, Pieter -- Borecki, Ingrid B -- Deloukas, Panos -- Fox, Caroline S -- Heid, Iris M -- O'Connell, Jeffrey R -- Strachan, David P -- Stefansson, Kari -- van Duijn, Cornelia M -- Abecasis, Goncalo R -- Franke, Lude -- Frayling, Timothy M -- McCarthy, Mark I -- Visscher, Peter M -- Scherag, Andre -- Willer, Cristen J -- Boehnke, Michael -- Mohlke, Karen L -- Lindgren, Cecilia M -- Beckmann, Jacques S -- Barroso, Ines -- North, Kari E -- Ingelsson, Erik -- Hirschhorn, Joel N -- Loos, Ruth J F -- Speliotes, Elizabeth K -- 084766/Wellcome Trust/United Kingdom -- 085235/Wellcome Trust/United Kingdom -- 097117/Wellcome Trust/United Kingdom -- 098381/Wellcome Trust/United Kingdom -- 14136/Cancer Research UK/United Kingdom -- CZB/4/672/Chief Scientist Office/United Kingdom -- CZB/4/710/Chief Scientist Office/United Kingdom -- G0601261/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- K01 HL116770/HL/NHLBI NIH HHS/ -- K23 DK080145/DK/NIDDK NIH HHS/ -- MC_PC_U127561128/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_UU_12015/1/Medical Research Council/United Kingdom -- MC_UU_12015/2/Medical Research Council/United Kingdom -- MC_UU_12015/5/Medical Research Council/United Kingdom -- MR/K013351/1/Medical Research Council/United Kingdom -- P20 MD006899/MD/NIMHD NIH HHS/ -- P30 DK020541/DK/NIDDK NIH HHS/ -- P30 DK020572/DK/NIDDK NIH HHS/ -- P30 DK063491/DK/NIDDK NIH HHS/ -- P30 GM103341/GM/NIGMS NIH HHS/ -- P30 HL107251/HL/NHLBI NIH HHS/ -- P60 DK020541/DK/NIDDK NIH HHS/ -- R01 AG041517/AG/NIA NIH HHS/ -- R01 DK062370/DK/NIDDK NIH HHS/ -- R01 DK072193/DK/NIDDK NIH HHS/ -- R01 DK075787/DK/NIDDK NIH HHS/ -- R01 DK078150/DK/NIDDK NIH HHS/ -- R01 DK089256/DK/NIDDK NIH HHS/ -- R01 DK093757/DK/NIDDK NIH HHS/ -- R01 HL109946/HL/NHLBI NIH HHS/ -- R01 HL117626/HL/NHLBI NIH HHS/ -- R21 DA027040/DA/NIDA NIH HHS/ -- T32 GM080178/GM/NIGMS NIH HHS/ -- T32 HL007055/HL/NHLBI NIH HHS/ -- T32 HL007824/HL/NHLBI NIH HHS/ -- TL1 TR001066/TR/NCATS NIH HHS/ -- U01 AG009740/AG/NIA NIH HHS/ -- U01 AG049505/AG/NIA NIH HHS/ -- U01 DK062370/DK/NIDDK NIH HHS/ -- U01 HG007416/HG/NHGRI NIH HHS/ -- U01 HG007419/HG/NHGRI NIH HHS/ -- UL1 TR000124/TR/NCATS NIH HHS/ -- UL1 TR001067/TR/NCATS NIH HHS/ -- UM1 CA182910/CA/NCI NIH HHS/ -- England -- Nature. 2015 Feb 12;518(7538):197-206. doi: 10.1038/nature14177.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Internal Medicine, Division of Gastroenterology, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. [4] Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby 2800, Denmark. ; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; 1] Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia. [2] The University of Queensland Diamantina Institute, The Translation Research Institute, Brisbane 4012, Australia. ; 1] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. [4] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. ; 1] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden. [2] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [3] Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden. ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; 1] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [2] Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden. ; 1] Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1010, Switzerland. [2] Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland. [3] Department of Medical Genetics, University of Lausanne, Lausanne 1005, Switzerland. ; 1] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. ; Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, D-93053 Regensburg, Germany. ; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. ; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan 48104, USA. ; Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. ; 1] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [2] Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden. [3] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA. ; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. ; Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia 6008, Australia. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Molecular Epidemiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. ; 1] Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. [2] Kidney Epidemiology and Cost Center, University of Michigan, Ann Arbor, Michigan 48109, USA. ; 1] Department of Statistics &Biostatistics, Rutgers University, Piscataway, New Jersey 08854, USA. [2] Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA. ; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. [2] Department of Human Genetics, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] Department of Gastroenterology and Hepatology, Imperial College London, London W2 1PG, UK. [3] Institute of infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China. ; 1] Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. [2] Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva 1211, Switzerland. ; Department of Epidemiology Research, Statens Serum Institut, Copenhagen DK-2300, Denmark. ; Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Division of Cardiovacular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK. ; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; 1] Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, D-68187 Mannheim, Germany. [2] Department of Internal Medicine II, Ulm University Medical Centre, D-89081 Ulm, Germany. ; National Institute for Health and Welfare, FI-00271 Helsinki, Finland. ; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA. ; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands. ; 1] Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands. [2] Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. [3] Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia. ; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University Hospital Essen, 45147 Essen, Germany. ; 1] Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands. [2] Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. [3] Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London W12 0NN, UK. ; 1] Department of Clinical Sciences, Genetic &Molecular Epidemiology Unit, Lund University Diabetes Center, Skane University Hosptial, Malmo 205 02, Sweden. [2] Department of Public Health and Clinical Medicine, Unit of Medicine, Umea University, Umea 901 87, Sweden. [3] Department of Odontology, Umea University, Umea 901 85, Sweden. ; University of Eastern Finland, FI-70210 Kuopio, Finland. ; Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm 17176, Sweden. ; Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland 21225, USA. ; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17475 Greifswald, Germany. ; 1] Department of Cardiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. [2] Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; Department of Medical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands. ; 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. [2] Core Genotyping Facility, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA. ; 1] CNRS UMR 8199, F-59019 Lille, France. [2] European Genomic Institute for Diabetes, F-59000 Lille, France. [3] Universite de Lille 2, F-59000 Lille, France. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK. ; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. [2] Center for Medical Sytems Biology, 2300 RC Leiden, The Netherlands. ; Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. ; 1] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [2] Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden. [3] School of Health and Social Studies, Dalarna University, SE-791 88 Falun, Sweden. ; PathWest Laboratory Medicine of Western Australia, Nedlands, Western Australia 6009, Australia. ; 1] Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK. [2] NHS Blood and Transplant, Cambridge CB2 0PT, UK. ; Geriatric Unit, Azienda Sanitaria Firenze (ASF), 50125 Florence, Italy. ; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. ; USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City 6000, Philippines. ; 1] Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78227, USA. [2] Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4001, Australia. ; Department of Medical Sciences, Endocrinology, Diabetes and Metabolism, Uppsala University, Uppsala 75185, Sweden. ; Division of Endocrinology, Diabetes and Metabolism, Ulm University Medical Centre, D-89081 Ulm, Germany. ; 1] Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, D-04103 Leipzig, Germany. [2] Department of Medicine, University of Leipzig, D-04103 Leipzig, Germany. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA. ; Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, D-04103 Leipzig, Germany. ; LifeLines Cohort Study, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. ; Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway. ; 1] Department of Pediatrics, University of California Los Angeles, Torrance, California 90502, USA. [2] Transgenomics Institute, Los Angeles Biomedical Research Institute, Torrance, California 90502, USA. ; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK. ; Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, D-68187 Mannheim, Germany. ; Department of Dietetics-Nutrition, Harokopio University, 17671 Athens, Greece. ; Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. ; 1] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [2] Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [2] Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. [3] Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, Maryland 20892, USA. ; Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala 75185, Sweden. ; Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Stockholm 17177, Sweden. ; Kaiser Permanente, Division of Research, Oakland, California 94612, USA. ; Service of Therapeutic Education for Diabetes, Obesity and Chronic Diseases, Geneva University Hospital, Geneva CH-1211, Switzerland. ; 1] Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK. [2] National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK. ; 1] Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, D-93053 Regensburg, Germany. [2] Department of Nephrology, University Hospital Regensburg, D-93053 Regensburg, Germany. ; 1] Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS-Hospital Stralsund, D-17475 Greifswald, Germany. [2] German Center for Neurodegenerative Diseases (DZNE), Rostock, Greifswald, D-17475 Greifswald, Germany. ; 1] Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [3] German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany. ; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universitat Dresden, D-01307 Dresden, Germany. ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden. ; Institut inter Regional pour la Sante, Synergies, F-37520 La Riche, France. ; Department of Public Health and Clinical Medicine, Unit of Nutritional Research, Umea University, Umea 90187, Sweden. ; Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands. ; Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, Finland. ; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK. ; 1] National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts 01702, USA. [2] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. [3] Faculty of Psychology and Education, VU University Amsterdam, 1081BT Amsterdam, The Netherlands. ; 1] Deutsches Forschungszentrum fur Herz-Kreislauferkrankungen (DZHK) (German Research Centre for Cardiovascular Research), Munich Heart Alliance, D-80636 Munich, Germany. [2] Deutsches Herzzentrum Munchen, Technische Universitat Munchen, D-80636 Munich, Germany. ; Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim 7489, Norway. ; Biological Psychology, VU University Amsterdam, 1081BT Amsterdam, The Netherlands. ; 1] Department of Pulmonary Physiology and Sleep Medicine, Nedlands, Western Australia 6009, Australia. [2] School of Medicine and Pharmacology, University of Western Australia, Crawley 6009, Australia. ; Uppsala University, Department of Immunology, Genetics, Pathology, SciLifeLab, Rudbeck Laboratory, SE-751 85 Uppsala, Sweden. ; Department of Internal Medicine II, Ulm University Medical Centre, D-89081 Ulm, Germany. ; Hjelt Institute Department of Public Health, University of Helsinki, FI-00014 Helsinki, Finland. ; Department of Internal Medicine I, Ulm University Medical Centre, D-89081 Ulm, Germany. ; Finnish Institute of Occupational Health, FI-90100 Oulu, Finland. ; Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria. ; Institute of Human Genetics, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. ; Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala 75185, Sweden. ; Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada. ; Institute for Community Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. ; 1] The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. [2] The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva 1211, Switzerland. ; School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK. ; 1] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. [2] Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia. ; 1] Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. [2] Farr Institute of Health Informatics Research, University College London, London NW1 2DA, UK. ; 1] Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. [2] The Center for Observational Research, Amgen, Inc., Thousand Oaks, California 91320, USA. ; Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cagliari, Sardinia 09042, Italy. ; Center for Evidence-based Healthcare, University Hospital Carl Gustav Carus, Technische Universitat Dresden, D-01307 Dresden, Germany. ; 1] Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Deutsches Forschungszentrum fur Herz-Kreislauferkrankungen (DZHK) (German Research Centre for Cardiovascular Research), Munich Heart Alliance, D-80636 Munich, Germany. [3] Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universitat, D-81377 Munich, Germany. [4] Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universitat, D-81377 Munich, Germany. ; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia. ; Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland 21224, USA. ; 1] Department of Genomics, Life &Brain Center, University of Bonn, 53127 Bonn, Germany. [2] Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany. ; Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. ; 1] Department of Epidemiology and Biostatistics, Institute for Research in Extramural Medicine, Institute for Health and Care Research, VU University Medical Center, 1081BT Amsterdam, The Netherlands. [2] Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, 8036 Graz, Austria. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. [3] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. ; Department of Clinical Sciences, Genetic &Molecular Epidemiology Unit, Lund University Diabetes Center, Skane University Hosptial, Malmo 205 02, Sweden. ; Institute of Physiology, University Medicine Greifswald, D-17495 Karlsburg, Germany. ; 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. [2] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. ; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. ; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria. ; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA. ; National Cancer Institute, Bethesda, Maryland 20892, USA. ; 1] Icelandic Heart Association, Kopavogur 201, Iceland. [2] University of Iceland, Reykjavik 101, Iceland. ; 1] Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. [2] Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. ; Molecular &Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. ; deCODE Genetics, Amgen Inc., Reykjavik 101, Iceland. ; 1] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. [2] William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; 1] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [2] Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala 75144, Sweden. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK. ; Department of Public Health Sciences, Stritch School of Medicine, Loyola University of Chicago, Maywood, Illinois 61053, USA. ; 1] German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany. [2] Institute of Epidemiology II, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, Neuherberg, Germany, D-85764 Neuherberg, Germany. ; Department of Oncology, University of Cambridge, Cambridge CB2 0QQ, UK. ; Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 413 45, Sweden. ; Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC University Medical Centre, 3000 CB Rotterdam, The Netherlands. ; 1] Department for Health Evidence, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. [2] Department of Genetics, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. ; Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; Genetics, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA. ; 1] German Center for Cardiovascular Research, partner site Hamburg/Lubeck/Kiel, 23562 Lubeck, Germany. [2] Institut fur Integrative und Experimentelle Genomik, Universitat zu Lubeck, D-23562 Lubeck, Germany. ; Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, 9037 Tromso, Norway. ; MRC Unit for Lifelong Health and Ageing at University College London, London WC1B 5JU, UK. ; Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland. ; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea. ; Lady Davis Institute, Departments of Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal, Quebec H3T1E2, Canada. ; Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 17176, Sweden. ; Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA. ; 1] Biosciences Research Division, Department of Primary Industries, Victoria 3083, Australia. [2] Department of Food and Agricultural Systems, University of Melbourne, Victoria 3010, Australia. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China. ; 1] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. [2] NIHR Oxford Biomedical Research Centre, OUH Trust, Oxford OX3 7LE, UK. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [2] Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. ; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan. ; Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Chungbuk 363-951, Republic of Korea. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Harvard School of Public Health, Department of Biostatistics, Harvard University, Boston, Massachusetts 2115, USA. ; Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, New Haven, Connecticut 06520, USA. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] College of Information Science and Technology, Dalian Maritime University, Dalian, Liaoning 116026, China. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, County Down BT9 7AB, UK. ; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK. ; 1] National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts 01702, USA. [2] Section of General Internal Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA. ; 1] Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK. [2] MRC Harwell, Harwell Science and Innovation Campus, Harwell OX11 0QG, UK. ; 1] QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia. [2] Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia. ; 1] Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan. [2] Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. [3] Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; Genome Institute of Singapore, Agency for Science, Technology and Research, 138672 Singapore. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Biomedical Engineering and Computational Science, Aalto University School of Science, Helsinki FI-00076, Finland. [2] Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, FI-00290 Helsinki, Finland. [3] Folkhalsan Institute of Genetics, Folkhalsan Research Center, FI-00290 Helsinki, Finland. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan. ; 1] Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan. [2] Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan. [3] Division of Disease Diversity, Bioresource Research Center, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan. ; Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia. ; Division of Epidemiology, Department of Medicine; Vanderbilt Epidemiology Center; and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee 37075, USA. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Nuffield Department of Obstetrics &Gynaecology, University of Oxford, Oxford OX3 7BN, UK. ; Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Department of Epidemiology and Public Health, EA3430, University of Strasbourg, Faculty of Medicine, Strasbourg, France. ; Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands. ; 1] PathWest Laboratory Medicine of Western Australia, Nedlands, Western Australia 6009, Australia. [2] Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia 6009, Australia. ; Cedars-Sinai Diabetes and Obesity Research Institute, Los Angeles, California 90048, USA. ; Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78227, USA. ; 1] Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1010 Lausanne, Switzerland. [2] Ministry of Health, Victoria, Republic of Seychelles. ; University of Milano, Bicocca, 20126, Italy. ; Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; 1] Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA. [2] Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA. ; 1] National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts 01702, USA. [2] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; 1] Department of Health Sciences, University of Milano, I 20142, Italy. [2] Fondazione Filarete, Milano I 20139, Italy. ; Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. ; 1] Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. [2] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK. ; Clinic of Cardiology, West-German Heart Centre, University Hospital Essen, 45147 Essen, Germany. ; 1] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [2] Department of General Practice and Primary Health Care, University of Helsinki, FI-00290 Helsinki, Finland. [3] Unit of General Practice, Helsinki University Central Hospital, Helsinki 00290, Finland. ; 1] Department of Internal Medicine B, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (Deutsches Zentrum fur Herz-Kreislaufforschung - German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; 1] Department of Internal Medicine, University of Pisa, 56100 Pisa, Italy. [2] National Research Council Institute of Clinical Physiology, University of Pisa, 56124 Pisa, Italy. ; Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, 31400 Toulouse, France. ; Robertson Center for Biostatistics, University of Glasgow, Glasgow G12 8QQ, UK. ; UWI Solutions for Developing Countries, The University of the West Indies, Mona, Kingston 7, Jamaica. ; 1] Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands. [2] Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; NorthShore University HealthSystem, Evanston, IL 60201, University of Chicago, Chicago, Illinois, USA. ; Leeds MRC Medical Bioinformatics Centre, University of Leeds, Leeds LS2 9LU, UK. ; Institute of Biomedical &Clinical Science, University of Exeter, Barrack Road, Exeter EX2 5DW, UK. ; Center for Biomedicine, European Academy Bozen, Bolzano (EURAC), Bolzano 39100, Italy (affiliated institute of the University of Lubeck, D-23562 Lubeck, Germany). ; Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK. ; Department of Vascular Medicine, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands. ; Centre for Cardiovascular Genetics, Institute Cardiovascular Sciences, University College London, London WC1E 6JJ, UK. ; Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84108, USA. ; 1] Sansom Institute for Health Research, University of South Australia, Adelaide 5000, South Australia, Australia. [2] School of Population Health, University of South Australia, Adelaide 5000, South Australia, Australia. [3] South Australian Health and Medical Research Institute, Adelaide, South Australia 5000, Australia. [4] Population, Policy, and Practice, University College London Institute of Child Health, London WC1N 1EH, UK. ; 1] Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Hannover Unified Biobank, Hannover Medical School, Hannover, D-30625 Hannover, Germany. ; 1] Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK. [2] National Institute for Health and Welfare, FI-90101 Oulu, Finland. [3] MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK. [4] Unit of Primary Care, Oulu University Hospital, FI-90220 Oulu, Finland. [5] Institute of Health Sciences, University of Oulu, FI-90014 Oulu, Finland. [6] Institute of Health Sciences, University of Oulu, FI-90014 Oulu, Finland. ; 1] Department of Cardiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. [2] Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute Netherlands (ICIN), 3501 DG Utrecht, The Netherlands. [3] Interuniversity Cardiology Institute of the Netherlands (ICIN), 3501 DG Utrecht, The Netherlands. ; 1] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [2] Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland. [3] Hjelt Institute Department of Public Health, University of Helsinki, FI-00014 Helsinki, Finland. ; 1] Institute of Health Sciences, University of Oulu, FI-90014 Oulu, Finland. [2] Unit of Primary Health Care/General Practice, Oulu University Hospital, FI-90220 Oulu, Finland. ; 1] Department for Health Evidence, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. [2] Department of Urology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK. [3] Imperial College Healthcare NHS Trust, London W12 0HS, UK. ; 1] Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK. [2] Department of Biological and Social Epidemiology, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK. ; Department of Medicine, Kuopio University Hospital and University of Eastern Finland, FI-70210 Kuopio, Finland. ; 1] Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, Finland. [2] Department of Physiology, Institute of Biomedicine, University of Eastern Finland, Kuopio Campus, FI-70211 Kuopio, Finland. [3] Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, FI-70210 Kuopio, Finland. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK. ; Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine University of Tampere, FI-33520 Tampere, Finland. ; 1] Steno Diabetes Center A/S, Gentofte DK-2820, Denmark. [2] Lund University Diabetes Centre and Department of Clinical Science, Diabetes &Endocrinology Unit, Lund University, Malmo 221 00, Sweden. ; 1] Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Faculty of Medicine, Laval University, Quebec, QC G1V 0A6, Canada. [2] Institute of Nutrition and Functional Foods, Laval University, Quebec, QC G1V 0A6, Canada. ; Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA. ; Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA. ; Department of Surgery, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; 1] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [3] Department of Biostatistics, University of Liverpool, Liverpool L69 3GA, UK. ; Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] MRC Unit for Lifelong Health and Ageing at University College London, London WC1B 5JU, UK. ; Illumina, Inc, Little Chesterford, Cambridge CB10 1XL, UK. ; 1] Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Deutsches Forschungszentrum fur Herz-Kreislauferkrankungen (DZHK) (German Research Centre for Cardiovascular Research), Munich Heart Alliance, D-80636 Munich, Germany. [3] Institute of Epidemiology II, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, Neuherberg, Germany, D-85764 Neuherberg, Germany. ; University of Groningen, University Medical Center Groningen, Department of Pulmonary Medicine and Tuberculosis, Groningen, The Netherlands. ; 1] Center for Biomedicine, European Academy Bozen, Bolzano (EURAC), Bolzano 39100, Italy (affiliated institute of the University of Lubeck, D-23562 Lubeck, Germany). [2] Department of Neurology, General Central Hospital, Bolzano 39100, Italy. ; 1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; 1] Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, FI-20521 Turku, Finland. [2] Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, FI-20521 Turku, Finland. ; Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA. ; 1] Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA. [2] Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri 63110, USA. [3] Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; 1] Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri 63110, USA. [2] Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; 1] Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada. [2] Universite de Montreal, Montreal, Quebec H1T 1C8, Canada. ; Center for Systems Genomics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; 1] Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. [2] Croatian Centre for Global Health, Faculty of Medicine, University of Split, 21000 Split, Croatia. ; South Carelia Central Hospital, 53130 Lappeenranta, Finland. ; 1] Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universitat Dresden, D-01307 Dresden, Germany. [2] Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), 01307 Dresden, Germany. ; International Centre for Circulatory Health, Imperial College London, London W2 1PG, UK. ; 1] Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [2] Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [3] Geriatric Research and Education Clinical Center, Vetrans Administration Medical Center, Baltimore, Maryland 21201, USA. ; Helsinki University Central Hospital Heart and Lung Center, Department of Medicine, Helsinki University Central Hospital, FI-00290 Helsinki, Finland. ; 1] Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universitat, D-81377 Munich, Germany. ; 1] Sorbonne Universites, UPMC Univ Paris 06, UMR S 1166, F-75013 Paris, France. [2] INSERM, UMR S 1166, Team Genomics and Physiopathology of Cardiovascular Diseases, F-75013 Paris, France. [3] Institute for Cardiometabolism And Nutrition (ICAN), F-75013 Paris, France. ; Department of Kinesiology, Laval University, Quebec QC G1V 0A6, Canada. ; Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita di Milano &Centro Cardiologico Monzino, Instituto di Ricovero e Cura a Carattere Scientifico, Milan 20133, Italy. ; 1] Institute of Nutrition and Functional Foods, Laval University, Quebec, QC G1V 0A6, Canada. [2] Department of Food Science and Nutrition, Laval University, Quebec QC G1V 0A6, Canada. ; 1] Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (Deutsches Zentrum fur Herz-Kreislaufforschung - German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; Department of Internal Medicine, University Hospital (CHUV) and University of Lausanne, Lausanne 1011, Switzerland. ; Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; Institut Pasteur de Lille; INSERM, U744; Universite de Lille 2; F-59000 Lille, France. ; 1] Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK. [2] Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute Netherlands (ICIN), 3501 DG Utrecht, The Netherlands. [3] Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; Department of Medicine, Stanford University School of Medicine, Palo Alto, California 94304, USA. ; 1] Lee Kong Chian School of Medicine, Imperial College London and Nanyang Technological University, Singapore, 637553 Singapore, Singapore. [2] Department of Internal Medicine I, Ulm University Medical Centre, D-89081 Ulm, Germany. ; Health Science Center at Houston, University of Texas, Houston, Texas 77030, USA. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK. [3] Imperial College Healthcare NHS Trust, London W12 0HS, UK. ; 1] Department of Medical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. [2] Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Department of Epidemiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; 1] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Department of Clinical Sciences, Genetic &Molecular Epidemiology Unit, Lund University Diabetes Center, Skane University Hosptial, Malmo 205 02, Sweden. [3] Department of Public Health and Clinical Medicine, Unit of Medicine, Umea University, Umea 901 87, Sweden. ; 1] Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London W12 0NN, UK. [2] CNRS UMR 8199, F-59019 Lille, France. [3] European Genomic Institute for Diabetes, F-59000 Lille, France. [4] Universite de Lille 2, F-59000 Lille, France. ; 1] Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland. [2] Lund University Diabetes Centre and Department of Clinical Science, Diabetes &Endocrinology Unit, Lund University, Malmo 221 00, Sweden. ; 1] PathWest Laboratory Medicine of Western Australia, Nedlands, Western Australia 6009, Australia. [2] Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia 6009, Australia. [3] School of Population Health, The University of Western Australia, Nedlands, Western Australia 6009, Australia. ; 1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [3] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; Albert Einstein College of Medicine, Department of Epidemiology and Population Health, Belfer 1306, New York 10461, USA. ; Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK. ; Center for Human Genetics, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA. ; 1] Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, D-68187 Mannheim, Germany. [2] Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria. [3] Synlab Academy, Synlab Services GmbH, 68163 Mannheim, Germany. ; 1] Department of Medicine, Stanford University School of Medicine, Palo Alto, California 94304, USA. [2] Department of Clinical Medicine, Copenhagen University, 2200 Copenhagen, Denmark. ; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. [2] Center for Medical Sytems Biology, 2300 RC Leiden, The Netherlands. [3] Department of Clinical Genetics, Erasmus MC University Medical Center, 3000 CA Rotterdam, The Netherlands. ; 1] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. [2] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [3] Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland. ; 1] Institute of Nutrition and Functional Foods, Laval University, Quebec, QC G1V 0A6, Canada. [2] Department of Kinesiology, Laval University, Quebec QC G1V 0A6, Canada. ; Population, Policy, and Practice, University College London Institute of Child Health, London WC1N 1EH, UK. ; 1] Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, Finland. [2] Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, FI-70210 Kuopio, Finland. ; 1] Finnish Diabetes Association, Kirjoniementie 15, FI-33680 Tampere, Finland. [2] Pirkanmaa Hospital District, FI-33521 Tampere, Finland. ; 1] Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. [2] Center for Non-Communicable Diseases, Karatchi, Pakistan. [3] Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; BHF Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK. ; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10580, USA. ; 1] deCODE Genetics, Amgen Inc., Reykjavik 101, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland. ; 1] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [2] Institute for Health Research, University Hospital of La Paz (IdiPaz), 28046 Madrid, Spain. [3] Diabetes Research Group, King Abdulaziz University, 21589 Jeddah, Saudi Arabia. [4] Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria. ; 1] Department of Public Health and Clinical Nutrition, University of Eastern Finland, Finland. [2] Research Unit, Kuopio University Hospital, FI-70210 Kuopio, Finland. ; 1] Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. [2] Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands. [3] Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute Netherlands (ICIN), 3501 DG Utrecht, The Netherlands. ; Institute of Cellular Medicine, Newcastle University, Newcastle NE1 7RU, UK. ; 1] DZHK (Deutsches Zentrum fur Herz-Kreislaufforschung - German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. [2] Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. ; 1] Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universitat, D-85764 Munich, Germany. [2] Klinikum Grosshadern, D-81377 Munich, Germany. [3] Institute of Epidemiology I, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, Neuherberg, Germany, D-85764 Neuherberg, Germany. ; Department of Pulmonology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; 1] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. [2] William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. [3] Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, 21589 Jeddah, Saudi Arabia. ; National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; 1] Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, D-93053 Regensburg, Germany. [2] Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. ; 1] Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [2] Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ; Division of Population Health Sciences &Education, St George's, University of London, London SW17 0RE, UK. ; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. [2] Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands. [3] Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. [4] Center for Medical Sytems Biology, 2300 RC Leiden, The Netherlands. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. [3] Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Trust, Oxford OX3 7LJ, UK. ; 1] Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University Hospital Essen, 45147 Essen, Germany. [2] Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, 07743 Jena, Germany. ; 1] Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. [2] Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA. [3] Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; 1] Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland. [2] Department of Medical Genetics, University of Lausanne, Lausanne 1005, Switzerland. [3] Service of Medical Genetics, CHUV University Hospital, 1011 Lausanne, Switzerland. ; 1] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. [2] University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 OQQ, UK. [3] NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 OQQ, UK. ; 1] Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. [2] Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. [3] The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. [4] The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25673413" target="_blank"〉PubMed〈/a〉
    Keywords: Adipogenesis/genetics ; Adiposity/genetics ; Age Factors ; *Body Mass Index ; Continental Population Groups/genetics ; Energy Metabolism/genetics ; Europe/ethnology ; Female ; Genetic Predisposition to Disease/genetics ; *Genome-Wide Association Study ; Glutamic Acid/metabolism ; Humans ; Insulin/metabolism/secretion ; Male ; Obesity/*genetics/*metabolism ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; Synapses/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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