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 language | English |
|---|---|
| Pages (from-to) | 937-948 |
| Number of pages | 12 |
| Journal | Nature Genetics |
| Volume | 42 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2010 |
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In: Nature Genetics, Vol. 42, No. 11, 01.11.2010, p. 937-948.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
AU - Speliotes, Elizabeth K.
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AU - Guiducci, Candace
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AU - Jewell, Eelizabeth
AU - John, Ulrich
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AU - Kajantie, Eeero
AU - Kaplan, Lee
AU - Kathiresan, Sekar
AU - Kettunen, Johannes
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AU - Kolcic, Ivana
AU - König, Inke R.
AU - Koskinen, Seppo
AU - Kovacs, Peter
AU - Kusisto, Johanna
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AU - Kvaløy, Kirsti
AU - Laitinen, Jaana
AU - Lantieri, Olivier
AU - Lanzani, Chiara
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AU - Lecoeur, Cecile
AU - Lehtimäki, Terho
AU - Lettre, Guillaume
AU - Liu, Jianjun
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AU - Lorentzon, Mattias
AU - Luben, Robert
AU - Ludwig, Barbara
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AU - Manunta, Paolo
AU - Marek, Diana
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AU - Martin, Nicholas G.
AU - McArdle, Wendy
AU - McCarthy, Anne
AU - McKnight, Barbara
AU - Meitinger, Thomas
AU - Melander, Olle
AU - Meyre, David
AU - Midthjell, Kristian
AU - Montgomery, Grant
AU - Morken, Mario A.
AU - Morris, Andrew P.
AU - Mulic, Rosanda
AU - Ngwa, Julius
AU - Nelis, Mari
AU - Neville, Matt J.
AU - Nyholt, Dale R.
AU - O'Ddonnell, Christopher J.
AU - O'Rahilly, Stephen
AU - Ong, Ken
AU - Ostra, Ben
AU - Paré, Guillaume
AU - Parker, Alex
AU - Perola, Markus
AU - Pichler, Irene
AU - Pietiläinen, Kirsi H.
AU - Platou, Carl P.
AU - Polasek, Ozren
AU - Pouta, Anneli
AU - Rafelt, Suzanne
AU - Raitakari, Olli
AU - Rayner, Nigel
AU - Ridderstråle, Martin
AU - Rief, Winfried
AU - Ruokonen, Aimo
AU - Robertson, Neil R.
AU - Rzehak, Peter
AU - Salomaa, Veikko
AU - Sanders, Alan R.
AU - Sandhu, Manjinder
AU - Sanna, Serena
AU - Saramies, Jouko
AU - Savolainen, Markku J.
AU - Scherag, Susann
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AU - Schreiber, Stefan
AU - Schunkert, Heribert
AU - Silander, Kaisa
AU - Sinisalo, Juha
AU - Siscovick, David S.
AU - Smit, Jan H.
AU - Soranzo, Nicole
AU - Sovio, Ulla
AU - Stephens, Jonathan
AU - Surakka, Ida
AU - Swift, Amy J.
AU - Tammesoo, Mari Lliis
AU - Tardif, Jean Claude
AU - Teder-Laving, Maris
AU - Teslovich, Tanya
AU - Thompson, John R.
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AU - Tuomi, Tiinamaija
AU - Van Meurs, Joyce B.J.
AU - Van OMen, Gert Jan
AU - Vatin, Vincent
AU - Viikari, Jorma
AU - Visvikis-Siest, Sophie
AU - Vitart, Veronique
AU - Vogel, Carla I.
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AU - Waite, Lindsay
AU - Wallaschofski, Henri
AU - Walters, Bragi
AU - Widen, Elisabeth
AU - Wiegand, Susanna
AU - Wild, Sarah H.
AU - Willemsen, Gonneke
AU - Witte, Deniel R.
AU - Witteman, Jacqueline
AU - Xu, Jianfeng
AU - Zhang, Qunyuan
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AU - Huikuri, Heikki V.
AU - James, Alan
AU - Kähönen, Mika
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AU - MacCiardi, Fabio
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AU - Boerwinkle, Eeric
AU - BOmsma, Dorret I.
AU - Caulfield, Mark J.
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AU - Cupples, L. Adrienne
AU - Smith, George Davey
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AU - Gyllensten, Ulf
AU - Hall, Per
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AU - Hattersley, Andrew T.
AU - Hayes, Richard B.
AU - Heinrich, Joachim
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AU - Hveem, Kristian
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AU - Lawlor, Debbie A.
AU - Metspalu, Andres
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AU - Rudan, Igor
AU - Samani, Nilesh J.
AU - Schwarz, Peter E.H.
AU - Shuldiner, Alan R.
AU - Spector, Timothy D.
AU - Tuomilehto, Jaakko
AU - Uda, Manuela
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AU - Valle, Timo
AU - Wabitsch, Martin
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AU - Wareham, Nicholas J.
AU - Watkins, Hugh
AU - Wilson, James F.
AU - Wright, Alan F.
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AU - Fox, Caroline S.
AU - Groop, Leif C.
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AU - Kaplan, Robert
AU - Mohlke, Karen
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AU - Wichmann, H. Erich
AU - Frayling, Timothy M.
AU - Thorsteinsdottir, Unnur
AU - Abecasis, Gonçalo R.
AU - Barroso, Inês
AU - Boehnke, Michael
AU - StefanSon, Kari
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AU - McArthy, Mark I.
AU - Hirschhorn, Joel N.
AU - IngelSon, Erik
AU - Loos, Ruth J.F.
N1 - 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
PY - 2010/11/1
Y1 - 2010/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78049337953&partnerID=8YFLogxK
U2 - 10.1038/ng.686
DO - 10.1038/ng.686
M3 - Article
C2 - 20935630
AN - SCOPUS:78049337953
SN - 1061-4036
VL - 42
SP - 937
EP - 948
JO - Nature Genetics
JF - Nature Genetics
IS - 11
ER -