Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Elizabeth K. Speliotes, Cristen J. Willer, Sonja I. Berndt, Keri L. Monda, Gudmar Thorleifsson, Anne U. Jackson, Hana Lango Allen, Cecilia M. Lindgren, Jian'An Luan, Reedik Mägi, Joshua C. Randall, Sailaja Vedantam, Thomas W. Winkler, Lu Qi, Tsegaselassie Workalemahu, Iris Heid, Valgerdur Steinthorsdottir, Heather Stringham, Michael N. Weedon, Eeleanor WheelerAndrew R. Wood, Teresa Ferreira, Robert J. Weyant, Ayellet V. Segrè, Karol Eestrada, Liming Liang, James Nemesh, Ju Hyun Park, Stefan Gustafsson, Tuomas O. Kilpeläinen, Jian Yang, Nabila Bouatia-Naji, Tõnu Eesko, Mary F. Feitosa, Zoltán Kutalik, Massimo Mangino, Soumya Raychaudhuri, Andre Scherag, Albert Vernon Smith, Ryan Welch, Jing Hua Zhao, Katja K. Aben, Devin M. Absher, Najaf Amin, Anna L. Dixon, Eeva Fisher, Nicole Glazer, Michael E. Goddard, Nancy Heard-Costa, Volker Hoesel, Jouke Jan Hottenga, Åsa Johansson, Toby Johnson, Shamika Ketkar, Claudia Lamina, Shengxu Li, Miriam F. Moffatt, Richard H. Myers, Narisu Narisu, John R B Perry, Marjolein J. Peters, Micheal Preuss, Samuli Ripatti, Fernando Rivadeneira, Camilla Sandholt, Laura J. Scott, Nicholas J. Timpson, Jonathan P. Tyrer, Sophie Van Wingerden, Richard Watanabe, Charles C. White, Fredrik Wiklund, Christina Barlassina, Daniel I. Chasman, Matthew N. Cooper, John Olov Jansson, Robert W. Lawrence, Niina Pellikka, Inga Prokopenko, Jianxin Shi, Eelisabeth Thiering, Helene Alavere, Maria T S Alibrandi, Peter Almgren, Alice Arnold, Thor Aspelund, Larry D. Atwood, Beverley Balkau, Anthony J. Balmforth, Amanda J. Bennett, Yoav Ben-Shlomo, Richard Bergman, Sven Bergmann, Heike Biebermann, Alexandra I F Blakemore, Tanja Boes, Lori Bonnycastle, Stefan R. Bornstein, Morris J. Brown, Thomas A. Buchanan, Fabio Busonero, Harry Campbell, Francesco P. Cappuccio, Christine Cavalcanti-Proença, Yii Dder Ida Chen, Chih Mei Chen, Peter Chines, Robert Clarke, Lachlan Coin, John Connell, Ian Day, Martin Den Heijer, Jubao Duan, Shah Eebrahim, Paul Eelliott, Roberto Eelosua, Gudny Eeiriksdottir, Micheal R. Eerdos, Johan G. Eeriksson, Maurizio F. Facheris, Stephan B. Felix, Pamela Fischer-Posovszky, Aaron R. Folsom, Nele Friedrich, Nelson B. Freimer, Mao Fu, Stefan Gaget, Pablo V. Gejman, Eeco J. Geus, Christian Gieger, Anette P. Gjesing, Anuj Goel, Philippe Goyette, Harald Grallert, Jürgen Gräßler, Danielle Greenawalt, Christopher J. Groves, Vilmundur Gudnason, Candace Guiducci, Anna Lliisa Hartikainen, Neelam Hassanali, Alistair Hall, Aki Havulinna, Caroline Hayward, Andrew Heath, Christian Hengstenberg, Andrew A. Hicks, Anke Hinney, Albert Hofman, Georg Homuth, Jennie Hui, Wilmar Igl, Carlos Iribarren, Bo Isomaa, Kevin B. Jacobs, Ivonne Jarick, Eelizabeth Jewell, Ulrich John, Torben Jørgensen, Pekka Jousilahti, Antti Jula, Marika Kaakinen, Eeero Kajantie, Lee Kaplan, Sekar Kathiresan, Johannes Kettunen, Leena Kinnunen, Joshua Knowles, Ivana Kolcic, Inke R. König, Seppo Koskinen, Peter Kovacs, Johanna Kusisto, Peter Kraft, Kirsti Kvaløy, Jaana Laitinen, Olivier Lantieri, Chiara Lanzani, Lenore J. Launer, Cecile Lecoeur, Terho Lehtimäki, Guillaume Lettre, Jianjun Liu, Marja Lissa Lokki, Mattias Lorentzon, Robert Luben, Barbara Ludwig, [No Value] Magic, Paolo Manunta, Diana Marek, Michel Marre, Nicholas G. Martin, Wendy McArdle, Anne McCarthy, Barbara McKnight, Thomas Meitinger, Olle Melander, David Meyre, Kristian Midthjell, Grant Montgomery, Mario A. Morken, Andrew P. Morris, Rosanda Mulic, Julius Ngwa, Mari Nelis, Matt J. Neville, Dale R. Nyholt, Christopher J. O'Ddonnell, Stephen O'Rahilly, Ken Ong, Ben Ostra, Guillaume Paré, Alex Parker, Markus Perola, Irene Pichler, Kirsi H. Pietiläinen, Carl P. Platou, Ozren Polasek, Anneli Pouta, Suzanne Rafelt, Olli Raitakari, Nigel Rayner, Martin Ridderstråle, Winfried Rief, Aimo Ruokonen, Neil R. Robertson, Peter Rzehak, Veikko Salomaa, Alan R. Sanders, Manjinder Sandhu, Serena Sanna, Jouko Saramies, Markku J. Savolainen, Susann Scherag, Sabine Schipf, Stefan Schreiber, Heribert Schunkert, Kaisa Silander, Juha Sinisalo, David S. Siscovick, Jan H. Smit, Nicole Soranzo, Ulla Sovio, Jonathan Stephens, Ida Surakka, Amy J. Swift, Mari Lliis Tammesoo, Jean Claude Tardif, Maris Teder-Laving, Tanya Teslovich, John R. Thompson, Brian Thomson, Anke Tönjes, Tiinamaija Tuomi, Joyce B J Van Meurs, Gert Jan Van OMen, Vincent Vatin, Jorma Viikari, Sophie Visvikis-Siest, Veronique Vitart, Carla I. Vogel, Benjamin F. Voight, Lindsay Waite, Henri Wallaschofski, Bragi Walters, Elisabeth Widen, Susanna Wiegand, Sarah H. Wild, Gonneke Willemsen, Deniel R. Witte, Jacqueline Witteman, Jianfeng Xu, Qunyuan Zhang, Lina Zgaga, Andreas Ziegler, Paavo Zitting, John P. Beilby, I. Ssadaf FarOqi, Johannes Hebebrand, Heikki V. Huikuri, Alan James, Mika Kähönen, Douglas F. Levinson, Fabio MacCiardi, Markku S. Nieminen, Claes Ohlsson, Lyle J. Palmer, Paul Ridker, Micheal Stumvoll, Jacques Beckmann, Heiner Boeing, Eeric Boerwinkle, Dorret I. BOmsma, Mark J. Caulfield, Stephan J. Chanock, Francis Collins, L. Adrienne Cupples, George Davey Smith, Jeanette Eerdmann, Philippe Frogue, Henrik Grönberg, Ulf Gyllensten, Per Hall, Torben Hansen, Tamara B. Harris, Andrew T. Hattersley, Richard B. Hayes, Joachim Heinrich, Frank B. Hu, Kristian Hveem, Thomas Illig, Marjo Riitta Jarvelin, Jaakko Kaprio, Fredrik Karpe, Kay Ttee Khaw, Lambertus A. Kiemeney, Heiko Krude, Markku Laakso, Debbie A. Lawlor, Andres Metspalu, Patricia B. Munroe, Willem H. Ouwehand, Oluf Pedersen, Brenda W. Penninx, Annette Peters, Peter P. Pramstaller, Thomas Quertermous, Thomas Reinehr, Aila Rissanen, Igor Rudan, Nilesh J. Samani, Peter E H Schwarz, Alan R. Shuldiner, Timothy D. Spector, Jaakko Tuomilehto, Manuela Uda, André Uitterlinden, Timo Valle, Martin Wabitsch, Gérard Waeber, Nicholas J. Wareham, Hugh Watkins, James F. Wilson, Alan F. Wright, M. Ccarola Zillikens, Nilanjan ChatterjE, Steven A. McCarroll, Shaun Purcell, Eric Schadt, Peter Visscher, Themistocles L. Assimes, Ingrid B. Borecki, Panos Deloukas, Caroline S. Fox, Leif C. Groop, Talin Haritunians, David J. Hunter, Robert Kaplan, Karen Mohlke, Jeffrey R. O'ConneL, Leena Peltonen, David SchleSinger, David P. P Strachan, Cornelia Van Duijn, H. Erich Wichmann, Timothy M. Frayling, Unnur Thorsteinsdottir, Gonçalo R. Abecasis, Inês Barroso, Michael Boehnke, Kari StefanSon, Kari E. North, Mark I. McArthy, Joel N. Hirschhorn, Erik IngelSon, Ruth J F Loos

Research output: Contribution to journalArticlepeer-review

2058 Scopus citations

Abstract

Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS index (P < 5-10-8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly aSociated loci may provide new insights into human body weight regulation.

Original languageEnglish (US)
Pages (from-to)937-948
Number of pages12
JournalNature Genetics
Volume42
Issue number11
DOIs
StatePublished - Nov 1 2010

Bibliographical note

Funding Information:
Funding was provided by Academy of Finland (10404, 77299, 104781, 114382, 117797, 120315, 121584, 124243, 126775, 126925, 127437, 129255, 129269, 129306, 129494, 129680, 130326, 209072, 210595, 213225, 213506 and 216374); ADA Mentor-Based Postdoctoral Fellowship; Amgen; Agency for Science, Technology and Research of Singapore (A*STAR); ALF/LUA research grant in Gothenburg; Althingi (the Icelandic Parliament); AstraZeneca; Augustinus Foundation; Australian National Health and Medical Research Council (241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688, 552485 and 613672); Australian Research Council (ARC grant DP0770096); Becket Foundation; Biocenter (Finland); Biomedicum Helsinki Foundation; Boston Obesity Nutrition Research Center; British Diabetes Association (1192); British Heart Foundation (97020; PG/02/128); Busselton Population Medical Research Foundation; Cambridge Institute for Medical Research; Cambridge National Institute of Health Research (NIHR) Comprehensive Biomedical Research Centre; CamStrad (UK); Cancer Research UK; Centre for Medical Systems Biology (The Netherlands); Centre for Neurogenomics and Cognitive Research (The Netherlands); Chief Scientist Office of the Scottish Government; Contrat Plan Etat Région (France); Danish Centre for Health Technology Assessment; Danish Diabetes Association; Danish Heart Foundation; Danish Pharmaceutical Association; Danish Research Council; Deutsche Forschungsgemeinschaft (DFG; HE 1446/4-1); Department of Health (UK); Diabetes UK; Diabetes and Inflammation Laboratory; Donald W. Reynolds Foundation; Dresden University of Technology Funding Grant; Emil and Vera Cornell Foundation; Erasmus Medical Center (Rotterdam); Erasmus University (Rotterdam); European Commission (DG XII; QLG1-CT-2000-01643, QLG2-CT-2002-01254, LSHC-CT-2005, LSHG-CT-2006-018947, LSHG-CT-2004-518153, LSH-2006-037593, LSHM-CT-2007-037273, HEALTH-F2-2008-ENGAGE, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550, FP7/2007-2013, 205419, 212111, 245536, SOC 95201408 05F02 and WLRT-2001-01254); Federal Ministry of Education and Research (Germany) (01AK803, 01EA9401, 01GI0823, 01GI0826, 01GP0209, 01GP0259, 01GS0820, 01GS0823, 01GS0824, 01GS0825, 01GS0830, 01GS0831, 01IG07015, 01KU0903, 01ZZ9603, 01ZZ0103, 01ZZ0403 and 03ZIK012); Federal State of Mecklenburg-West Pomerania; European Social Fund; Eve Appeal; Finnish Diabetes Research Foundation; Finnish Foundation for Cardiovascular Research; Finnish Foundation for Pediatric Research, Finnish Medical Society; Finska Läkaresällskapet, Päivikki and Sakari Sohlberg Foundation, Folkhälsan Research Foundation; Fond Européen pour le Développement Régional (France); Fondation LeDucq (Paris, France); Foundation for Life and Health in Finland; Foundation for Strategic Research (Sweden); Genetic Association Information Network; German Research Council (KFO-152); German National Genome Research Net ‘NGFNplus’ (FKZ 01GS0823); German Research Center for Environmental Health; Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Göteborg Medical Society; Great Wine Estates Auctions; Gyllenberg Foundation; Health Care Centers in Vasa, Närpes and Korsholm; Healthway, Western Australia; Helmholtz Center Munich; Helsinki University Central Hospital, Hjartavernd (the Icelandic Heart Association); INSERM (France); Ib Henriksen Foundation; Interdisziplinäres Zentrum für Klinische Forschung (IZKF) (B27); Jalmari and Rauha Ahokas Foundation; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International (JDRF); Karolinska Institute; Knut and Alice Wallenberg Foundation; Leenaards Foundation; Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LUCAMP); Lundberg Foundation; Marie Curie Intra-European Fellowship; Medical Research Council (UK) (G0000649, G0000934, G9521010D, G0500539, G0600331 and G0601261, PrevMetSyn); Ministry of Cultural Affairs and Social Ministry of the Federal State of Mecklenburg-West Pomerania; Ministry for Health, Welfare and Sports (The Netherlands); Ministry of Education (Finland); Ministry of Education, Culture and Science (The Netherlands); Ministry of Internal Affairs and Health (Denmark); Ministry of Science, Education and Sport of the Republic of Croatia (216-1080315-0302); Ministry of Science, Research and the Arts Baden-Württemberg; Montreal Heart Institute Foundation; Municipal Health Care Center and Hospital in Jakobstad; Municipality of Rotterdam; Närpes Health Care Foundation; National Cancer Institute; National Health and Medical Research Council of Australia; National Institute for Health Research Cambridge Biomedical Research Centre; National Institute for Health Research Oxford Biomedical Research Centre; National Institute for Health Research comprehensive Biomedical Research Centre; US National Institutes of Health (263-MA-410953, AA07535, AA10248, AA014041, AA13320, AA13321, AA13326, CA047988, CA65725, CA87969, CA49449, CA67262, CA50385, DA12854, DK58845, DK46200, DK062370, DK063491, DK072193, HG002651, HL084729, HHSN268200625226C, HL71981, K23-DK080145, K99-HL094535, M01-RR00425, MH084698, N01-AG12100, NO1-AG12109, N01-HC15103, N01-HC25195, N01-HC35129, N01-HC45133, N01-HC55015, N01-HC55016, N01-HC55018, N01-HC55019, N01-HC55020, N01-N01HC-55021, N01-HC55022, N01-HC55222, N01-HC75150, N01-HC85079, N01-HC85080, N01-HG-65403, N01-HC85081, N01-HC85082, N01-HC85083, N01-HC85084, N01-HC85085, N01-HC85086, N02-HL64278, P30-DK072488, R01-AG031890, R01-DK073490, R01-DK075787, R01DK068336, R01DK075681, R01-HL59367, R01-HL086694, R01-HL087641, R01-HL087647, R01-HL087652, R01-HL087676, R01-HL087679, R01-HL087700, R01-HL088119, R01-MH59160, R01-MH59565, R01-MH59566, R01-MH59571, R01-MH59586, R01-MH59587, R01-MH59588, R01-MH60870, R01-MH60879, R01-MH61675, R01-MH63706, R01-MH67257, R01-MH79469, R01-MH79470, R01-MH81800, RL1-MH083268, UO1-CA098233, U01-DK062418, U01-GM074518, U01-HG004402, U01-HG004399, U01-HL72515, U01-HL080295, U01-HL084756, U54-RR020278, T32-HG00040, UL1-RR025005 and Z01-HG000024); National Alliance for Research on Schizophrenia and Depression (NARSAD); Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging (050-060-810); Netherlands Organisation for Scientific Research (NWO) (904-61-090, 904-61-193, 480-04-004, 400-05-717, SPI 56-464-1419, 175.010.2005.011 and 911-03-012); Nord-Trøndelag County Council; Nordic Center of Excellence in Disease Genetics; Novo Nordisk Foundation; Norwegian Institute of Public Health; Ollqvist Foundation; Oxford NIHR Biomedical Research Centre; Organization for the Health Research and Development (10-000-1002); Paavo Nurmi Foundation; Paul Michael Donovan Charitable Foundation; Perklén Foundation; Petrus and Augusta Hedlunds Foundation; Pew Scholar for the Biomedical Sciences; Public Health and Risk Assessment, Health and Consumer Protection (2004310); Research Foundation of Copenhagen County; Research Institute for Diseases in the Elderly (014-93-015; RIDE2); Robert Dawson Evans Endowment; Royal Society (UK); Royal Swedish Academy of Science; Sahlgrenska Center for Cardiovascular and Metabolic Research (CMR, no. A305: 188); Siemens Healthcare, Erlangen, Germany; Sigrid Juselius Foundation; Signe and Ane Gyllenberg Foundation; Science Funding programme (UK); Social Insurance Institution of Finland; Söderberg’s Foundation; South Tyrol Ministry of Health; South Tyrolean Sparkasse Foundation; State of Bavaria; Stockholm County Council (560183); Susan G. Komen Breast Cancer Foundation; Swedish Cancer Society; Swedish Cultural Foundation in Finland; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation; Swedish Medical Research Council (8691, K2007-66X-20270-01-3, K2010-54X-09894-19-3, K2010-54X-09894-19-3 and 2006-3832); Swedish Research Council; Swedish Society of Medicine; Swiss National Science Foundation

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