Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Cristen J. Willer; Elizabeth K. Speliotes; Ruth J.F. Loos; Shengxu Li; Cecilia M. Lindgren; Iris M. Heid; Sonja I. Berndt; Amanda L. Elliott; Anne U. Jackson; Claudia Lamina; Guillaume Lettre; Noha Lim; Helen N. Lyon; Steven A. McCarroll; Konstantinos Papadakis; Lu Qi; Joshua C. Randall; Rosa Maria Roccasecca; Serena Sanna; Paul Scheet; Michael N. Weedon; Eleanor Wheeler; Jing Hua Zhao; Leonie C. Jacobs; Inga Prokopenko; Nicole Soranzo; Toshiko Tanaka; Nicholas J. Timpson; Peter Almgren; Amanda Bennett; Richard N. Bergman; Sheila A. Bingham; Lori L. Bonnycastle; Morris Brown; Noël P. Burtt; Peter Chines; Lachlan Coin; Francis S. Collins; John M. Connell; Cyrus Cooper; George Davey Smith; Elaine M. Dennison; Parimal Deodhar; Paul Elliott; Michael R. Erdos; Karol Estrada; David M. Evans; Lauren Gianniny; Christian Gieger; Christopher J. Gillson; Candace Guiducci; Rachel Hackett; David Hadley; Alistair S. Hall; Aki S. Havulinna; Johannes Hebebrand; Albert Hofman; Bo Isomaa; Kevin B. Jacobs; Toby Johnson; Pekka Jousilahti; Zorica Jovanovic; Kay Tee Khaw; Peter Kraft; Mikko Kuokkanen; Johanna Kuusisto; Jaana Laitinen; Edward G. Lakatta; Jian'an Luan; Robert N. Luben; Massimo Mangino; Wendy L. McArdle; Thomas Meitinger; Antonella Mulas; Patricia B. Munroe; Narisu Narisu; Andrew R. Ness; Kate Northstone; Stephen O'Rahilly; Carolin Purmann; Matthew G. Rees; Martin Ridderstråle; Susan M. Ring; Fernando Rivadeneira; Aimo Ruokonen; Manjinder S. Sandhu; Jouko Saramies; Laura J. Scott; Angelo Scuteri; Kaisa Silander; Matthew A. Sims; Kijoung Song; Jonathan Stephens; Suzanne Stevens; Heather M. Stringham; Y. C.Loraine Tung; Timo T. Valle; Cornelia M. Van Duijn; Karani S. Vimaleswaran; Peter Vollenweider; Gerard Waeber; Chris Wallace; Richard M. Watanabe; Dawn M. Waterworth; Nicholas Watkins; Jacqueline C.M. Witteman; Eleftheria Zeggini; Guangju Zhai; M. Carola Zillikens; David Altshuler; Mark J. Caulfield; Stephen J. Chanock; I. Sadaf Farooqi; Luigi Ferrucci; Jack M. Guralnik; Andrew T. Hattersley; Frank B. Hu; Marjo Riitta Jarvelin; Markku Laakso; Vincent Mooser; Ken K. Ong; Willem H. Ouwehand; Veikko Salomaa; Nilesh J. Samani; Timothy D. Spector; Tiinamaija Tuomi; Jaakko Tuomilehto; Manuela Uda; André G. Uitterlinden; Nicholas J. Wareham; Panagiotis Deloukas; Timothy M. Frayling; Leif C. Groop; Richard B. Hayes; David J. Hunter; Karen L. Mohlke; Leena Peltonen; David Schlessinger; David P. Strachan; H. Erich Wichmann; Mark I. McCarthy; Michael Boehnke; Inês Barroso; Gonçalo R. Abecasis; Joel N. Hirschhorn

doi:10.1038/ng.287

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Cristen J. Willer, Elizabeth K. Speliotes, Ruth J.F. Loos, Shengxu Li, Cecilia M. Lindgren, Iris M. Heid, Sonja I. Berndt, Amanda L. Elliott, Anne U. Jackson, Claudia Lamina, Guillaume Lettre, Noha Lim, Helen N. Lyon, Steven A. McCarroll, Konstantinos Papadakis, Lu Qi, Joshua C. Randall, Rosa Maria Roccasecca, Serena Sanna, Paul ScheetMichael N. Weedon, Eleanor Wheeler, Jing Hua Zhao, Leonie C. Jacobs, Inga Prokopenko, Nicole Soranzo, Toshiko Tanaka, Nicholas J. Timpson, Peter Almgren, Amanda Bennett, Richard N. Bergman, Sheila A. Bingham, Lori L. Bonnycastle, Morris Brown, Noël P. Burtt, Peter Chines, Lachlan Coin, Francis S. Collins, John M. Connell, Cyrus Cooper, George Davey Smith, Elaine M. Dennison, Parimal Deodhar, Paul Elliott, Michael R. Erdos, Karol Estrada, David M. Evans, Lauren Gianniny, Christian Gieger, Christopher J. Gillson, Candace Guiducci, Rachel Hackett, David Hadley, Alistair S. Hall, Aki S. Havulinna, Johannes Hebebrand, Albert Hofman, Bo Isomaa, Kevin B. Jacobs, Toby Johnson, Pekka Jousilahti, Zorica Jovanovic, Kay Tee Khaw, Peter Kraft, Mikko Kuokkanen, Johanna Kuusisto, Jaana Laitinen, Edward G. Lakatta, Jian'an Luan, Robert N. Luben, Massimo Mangino, Wendy L. McArdle, Thomas Meitinger, Antonella Mulas, Patricia B. Munroe, Narisu Narisu, Andrew R. Ness, Kate Northstone, Stephen O'Rahilly, Carolin Purmann, Matthew G. Rees, Martin Ridderstråle, Susan M. Ring, Fernando Rivadeneira, Aimo Ruokonen, Manjinder S. Sandhu, Jouko Saramies, Laura J. Scott, Angelo Scuteri, Kaisa Silander, Matthew A. Sims, Kijoung Song, Jonathan Stephens, Suzanne Stevens, Heather M. Stringham, Y. C.Loraine Tung, Timo T. Valle, Cornelia M. Van Duijn, Karani S. Vimaleswaran, Peter Vollenweider, Gerard Waeber, Chris Wallace, Richard M. Watanabe, Dawn M. Waterworth, Nicholas Watkins, Jacqueline C.M. Witteman, Eleftheria Zeggini, Guangju Zhai, M. Carola Zillikens, David Altshuler, Mark J. Caulfield, Stephen J. Chanock, I. Sadaf Farooqi, Luigi Ferrucci, Jack M. Guralnik, Andrew T. Hattersley, Frank B. Hu, Marjo Riitta Jarvelin, Markku Laakso, Vincent Mooser, Ken K. Ong, Willem H. Ouwehand, Veikko Salomaa, Nilesh J. Samani, Timothy D. Spector, Tiinamaija Tuomi, Jaakko Tuomilehto, Manuela Uda, André G. Uitterlinden, Nicholas J. Wareham, Panagiotis Deloukas, Timothy M. Frayling, Leif C. Groop, Richard B. Hayes, David J. Hunter, Karen L. Mohlke, Leena Peltonen, David Schlessinger, David P. Strachan, H. Erich Wichmann, Mark I. McCarthy, Michael Boehnke, Inês Barroso, Gonçalo R. Abecasis, Joel N. Hirschhorn

Research output: Contribution to journal › Article › peer-review

1278 Scopus citations

Abstract

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 × 10^-8): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Original language	English (US)
Pages (from-to)	25-34
Number of pages	10
Journal	Nature genetics
Volume	41
Issue number	1
DOIs	https://doi.org/10.1038/ng.287
State	Published - Jan 2009
Externally published	Yes

ASJC Scopus subject areas

Genetics

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10.1038/ng.287

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Willer, C. J., Speliotes, E. K., Loos, R. J. F., Li, S., Lindgren, C. M., Heid, I. M., Berndt, S. I., Elliott, A. L., Jackson, A. U., Lamina, C., Lettre, G., Lim, N., Lyon, H. N., McCarroll, S. A., Papadakis, K., Qi, L., Randall, J. C., Roccasecca, R. M., Sanna, S., ... Hirschhorn, J. N. (2009). Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nature genetics, 41(1), 25-34. https://doi.org/10.1038/ng.287

Willer, CJ, Speliotes, EK, Loos, RJF, Li, S, Lindgren, CM, Heid, IM, Berndt, SI, Elliott, AL, Jackson, AU, Lamina, C, Lettre, G, Lim, N, Lyon, HN, McCarroll, SA, Papadakis, K, Qi, L, Randall, JC, Roccasecca, RM, Sanna, S, Scheet, P, Weedon, MN, Wheeler, E, Zhao, JH, Jacobs, LC, Prokopenko, I, Soranzo, N, Tanaka, T, Timpson, NJ, Almgren, P, Bennett, A, Bergman, RN, Bingham, SA, Bonnycastle, LL, Brown, M, Burtt, NP, Chines, P, Coin, L, Collins, FS, Connell, JM, Cooper, C, Smith, GD, Dennison, EM, Deodhar, P, Elliott, P, Erdos, MR, Estrada, K, Evans, DM, Gianniny, L, Gieger, C, Gillson, CJ, Guiducci, C, Hackett, R, Hadley, D, Hall, AS, Havulinna, AS, Hebebrand, J, Hofman, A, Isomaa, B, Jacobs, KB, Johnson, T, Jousilahti, P, Jovanovic, Z, Khaw, KT, Kraft, P, Kuokkanen, M, Kuusisto, J, Laitinen, J, Lakatta, EG, Luan, J, Luben, RN, Mangino, M, McArdle, WL, Meitinger, T, Mulas, A, Munroe, PB, Narisu, N, Ness, AR, Northstone, K, O'Rahilly, S, Purmann, C, Rees, MG, Ridderstråle, M, Ring, SM, Rivadeneira, F, Ruokonen, A, Sandhu, MS, Saramies, J, Scott, LJ, Scuteri, A, Silander, K, Sims, MA, Song, K, Stephens, J, Stevens, S, Stringham, HM, Tung, YCL, Valle, TT, Van Duijn, CM, Vimaleswaran, KS, Vollenweider, P, Waeber, G, Wallace, C, Watanabe, RM, Waterworth, DM, Watkins, N, Witteman, JCM, Zeggini, E, Zhai, G, Zillikens, MC, Altshuler, D, Caulfield, MJ, Chanock, SJ, Farooqi, IS, Ferrucci, L, Guralnik, JM, Hattersley, AT, Hu, FB, Jarvelin, MR, Laakso, M, Mooser, V, Ong, KK, Ouwehand, WH, Salomaa, V, Samani, NJ, Spector, TD, Tuomi, T, Tuomilehto, J, Uda, M, Uitterlinden, AG, Wareham, NJ, Deloukas, P, Frayling, TM, Groop, LC, Hayes, RB, Hunter, DJ, Mohlke, KL, Peltonen, L, Schlessinger, D, Strachan, DP, Wichmann, HE, McCarthy, MI, Boehnke, M, Barroso, I, Abecasis, GR & Hirschhorn, JN 2009, 'Six new loci associated with body mass index highlight a neuronal influence on body weight regulation', Nature genetics, vol. 41, no. 1, pp. 25-34. https://doi.org/10.1038/ng.287

@article{2fd5ed8ad0814994b1a43f3b66e74833,

title = "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation",

abstract = "Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 × 10-8): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.",

author = "Willer, {Cristen J.} and Speliotes, {Elizabeth K.} and Loos, {Ruth J.F.} and Shengxu Li and Lindgren, {Cecilia M.} and Heid, {Iris M.} and Berndt, {Sonja I.} and Elliott, {Amanda L.} and Jackson, {Anne U.} and Claudia Lamina and Guillaume Lettre and Noha Lim and Lyon, {Helen N.} and McCarroll, {Steven A.} and Konstantinos Papadakis and Lu Qi and Randall, {Joshua C.} and Roccasecca, {Rosa Maria} and Serena Sanna and Paul Scheet and Weedon, {Michael N.} and Eleanor Wheeler and Zhao, {Jing Hua} and Jacobs, {Leonie C.} and Inga Prokopenko and Nicole Soranzo and Toshiko Tanaka and Timpson, {Nicholas J.} and Peter Almgren and Amanda Bennett and Bergman, {Richard N.} and Bingham, {Sheila A.} and Bonnycastle, {Lori L.} and Morris Brown and Burtt, {No{\"e}l P.} and Peter Chines and Lachlan Coin and Collins, {Francis S.} and Connell, {John M.} and Cyrus Cooper and Smith, {George Davey} and Dennison, {Elaine M.} and Parimal Deodhar and Paul Elliott and Erdos, {Michael R.} and Karol Estrada and Evans, {David M.} and Lauren Gianniny and Christian Gieger and Gillson, {Christopher J.} and Candace Guiducci and Rachel Hackett and David Hadley and Hall, {Alistair S.} and Havulinna, {Aki S.} and Johannes Hebebrand and Albert Hofman and Bo Isomaa and Jacobs, {Kevin B.} and Toby Johnson and Pekka Jousilahti and Zorica Jovanovic and Khaw, {Kay Tee} and Peter Kraft and Mikko Kuokkanen and Johanna Kuusisto and Jaana Laitinen and Lakatta, {Edward G.} and Jian'an Luan and Luben, {Robert N.} and Massimo Mangino and McArdle, {Wendy L.} and Thomas Meitinger and Antonella Mulas and Munroe, {Patricia B.} and Narisu Narisu and Ness, {Andrew R.} and Kate Northstone and Stephen O'Rahilly and Carolin Purmann and Rees, {Matthew G.} and Martin Ridderstr{\aa}le and Ring, {Susan M.} and Fernando Rivadeneira and Aimo Ruokonen and Sandhu, {Manjinder S.} and Jouko Saramies and Scott, {Laura J.} and Angelo Scuteri and Kaisa Silander and Sims, {Matthew A.} and Kijoung Song and Jonathan Stephens and Suzanne Stevens and Stringham, {Heather M.} and Tung, {Y. C.Loraine} and Valle, {Timo T.} and {Van Duijn}, {Cornelia M.} and Vimaleswaran, {Karani S.} and Peter Vollenweider and Gerard Waeber and Chris Wallace and Watanabe, {Richard M.} and Waterworth, {Dawn M.} and Nicholas Watkins and Witteman, {Jacqueline C.M.} and Eleftheria Zeggini and Guangju Zhai and Zillikens, {M. Carola} and David Altshuler and Caulfield, {Mark J.} and Chanock, {Stephen J.} and Farooqi, {I. Sadaf} and Luigi Ferrucci and Guralnik, {Jack M.} and Hattersley, {Andrew T.} and Hu, {Frank B.} and Jarvelin, {Marjo Riitta} and Markku Laakso and Vincent Mooser and Ong, {Ken K.} and Ouwehand, {Willem H.} and Veikko Salomaa and Samani, {Nilesh J.} and Spector, {Timothy D.} and Tiinamaija Tuomi and Jaakko Tuomilehto and Manuela Uda and Uitterlinden, {Andr{\'e} G.} and Wareham, {Nicholas J.} and Panagiotis Deloukas and Frayling, {Timothy M.} and Groop, {Leif C.} and Hayes, {Richard B.} and Hunter, {David J.} and Mohlke, {Karen L.} and Leena Peltonen and David Schlessinger and Strachan, {David P.} and Wichmann, {H. Erich} and McCarthy, {Mark I.} and Michael Boehnke and In{\^e}s Barroso and Abecasis, {Gon{\c c}alo R.} and Hirschhorn, {Joel N.}",

note = "Funding Information: We are extremely grateful to all of the participants in each of the studies contributing to this effort. Full acknowledgments can be found in the Supplementary Note. Support for this research was provided by: US National Institutes of Health grants CA65725, CA87969, CA49449, CA67262, CA50385, DK062370, DK072193, DK075787, HG02651, HL084729, HL087679 (through STAMPEED, 1RL1MH083268), 5UO1CA098233, 1Z01 HG000024, 1RL1MH083268, T32 DK07191, F32 DK079466, K23 DK080145, K23 DK067288, CIDR NIH Contract Number N01-HG-65403, NIA contract NO1-AG-1-2109; the Intramural Research Program of the Division of Cancer Epidemiology and Genetics; contracts from the Division of Cancer Prevention, National Cancer Institute and EU FP6 funding (contract no LSHM-CT-2003-503041); GlaxoSmithKline; the Faculty of Biology and Medicine of Lausanne, Switzerland; the Intramural Research Program of the National Institute on Aging (NIA); Cancer Research United Kingdom; the UK Medical Research Council (including grants G0000649, G0000934 and G0601261); the Wellcome Trust (including Strategic Award 076113, grants 068545/Z/02 and 076467/Z/05/Z); the NIHR through the Biomedical Research Centres at Oxford, King{\textquoteright}s College London; Guys and St. Thomas{\textquoteright} Foundation Hospitals{\textquoteright} Trust; the British Heart Foundation (including grant FS/05/061/19501), European Community{\textquoteright}s Seventh Framework Programme (ENGAGE:HEALTH-F4-2007-201413); Diabetes UK; Unilever Corporate Research; American Diabetes Association including a Smith Family Foundation Pinnacle Program Project Award #7-03-PPG-04R; the Academy of Finland (grants 118065 and 124243); National Genome Research Net Germany; Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; the Helmholtz Center Munich; the Sigrid Juselius Foundation; University of Bristol; Linn{\'e} grant from Swedish Research Council; Wallenberg Foundation; Folkh{\"a}lsan Research Foundation; University of Southampton; Netherlands Organisation of Scientific Research NWO (nr. 175.010.2005.011); Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Ministry of Education, Culture and Science; the Netherlands Ministry for Health, Welfare and Sports; the European Commision (DG XII) and the Municipality of Rotterdam. G.R.A. and K.L.M. are Pew Scholars for the Biomedical Sciences; A.L.E. is supported by a Sarnoff Cardiovascular Research Foundation Fellowship; C.M.L. is a Nuffield Department of Medicine Scientific Leadership Fellow; S.A.M. is supported by a Life Sciences Research Fellowship; M.K. is supported by the Finnish Cultural Foundation; N.J.S. holds a BHF Chair; M.N.W. is a Vandervell Foundation Research Fellow; C.J.W. is supported by an American Diabetes Association postdoctoral fellowship; and E.Z. is a Wellcome Trust-RD Fellow (grant number 079557).",

year = "2009",

month = jan,

doi = "10.1038/ng.287",

language = "English (US)",

volume = "41",

pages = "25--34",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

AU - Willer, Cristen J.

AU - Speliotes, Elizabeth K.

AU - Loos, Ruth J.F.

AU - Li, Shengxu

AU - Lindgren, Cecilia M.

AU - Heid, Iris M.

AU - Berndt, Sonja I.

AU - Elliott, Amanda L.

AU - Jackson, Anne U.

AU - Lamina, Claudia

AU - Lettre, Guillaume

AU - Lim, Noha

AU - Lyon, Helen N.

AU - McCarroll, Steven A.

AU - Papadakis, Konstantinos

AU - Qi, Lu

AU - Randall, Joshua C.

AU - Roccasecca, Rosa Maria

AU - Sanna, Serena

AU - Scheet, Paul

AU - Weedon, Michael N.

AU - Wheeler, Eleanor

AU - Zhao, Jing Hua

AU - Jacobs, Leonie C.

AU - Prokopenko, Inga

AU - Soranzo, Nicole

AU - Tanaka, Toshiko

AU - Timpson, Nicholas J.

AU - Almgren, Peter

AU - Bennett, Amanda

AU - Bergman, Richard N.

AU - Bingham, Sheila A.

AU - Bonnycastle, Lori L.

AU - Brown, Morris

AU - Burtt, Noël P.

AU - Chines, Peter

AU - Coin, Lachlan

AU - Collins, Francis S.

AU - Connell, John M.

AU - Cooper, Cyrus

AU - Smith, George Davey

AU - Dennison, Elaine M.

AU - Deodhar, Parimal

AU - Elliott, Paul

AU - Erdos, Michael R.

AU - Estrada, Karol

AU - Evans, David M.

AU - Gianniny, Lauren

AU - Gieger, Christian

AU - Gillson, Christopher J.

AU - Guiducci, Candace

AU - Hackett, Rachel

AU - Hadley, David

AU - Hall, Alistair S.

AU - Havulinna, Aki S.

AU - Hebebrand, Johannes

AU - Hofman, Albert

AU - Isomaa, Bo

AU - Jacobs, Kevin B.

AU - Johnson, Toby

AU - Jousilahti, Pekka

AU - Jovanovic, Zorica

AU - Khaw, Kay Tee

AU - Kraft, Peter

AU - Kuokkanen, Mikko

AU - Kuusisto, Johanna

AU - Laitinen, Jaana

AU - Lakatta, Edward G.

AU - Luan, Jian'an

AU - Luben, Robert N.

AU - Mangino, Massimo

AU - McArdle, Wendy L.

AU - Meitinger, Thomas

AU - Mulas, Antonella

AU - Munroe, Patricia B.

AU - Narisu, Narisu

AU - Ness, Andrew R.

AU - Northstone, Kate

AU - O'Rahilly, Stephen

AU - Purmann, Carolin

AU - Rees, Matthew G.

AU - Ridderstråle, Martin

AU - Ring, Susan M.

AU - Rivadeneira, Fernando

AU - Ruokonen, Aimo

AU - Sandhu, Manjinder S.

AU - Saramies, Jouko

AU - Scott, Laura J.

AU - Scuteri, Angelo

AU - Silander, Kaisa

AU - Sims, Matthew A.

AU - Song, Kijoung

AU - Stephens, Jonathan

AU - Stevens, Suzanne

AU - Stringham, Heather M.

AU - Tung, Y. C.Loraine

AU - Valle, Timo T.

AU - Van Duijn, Cornelia M.

AU - Vimaleswaran, Karani S.

AU - Vollenweider, Peter

AU - Waeber, Gerard

AU - Wallace, Chris

AU - Watanabe, Richard M.

AU - Waterworth, Dawn M.

AU - Watkins, Nicholas

AU - Witteman, Jacqueline C.M.

AU - Zeggini, Eleftheria

AU - Zhai, Guangju

AU - Zillikens, M. Carola

AU - Altshuler, David

AU - Caulfield, Mark J.

AU - Chanock, Stephen J.

AU - Farooqi, I. Sadaf

AU - Ferrucci, Luigi

AU - Guralnik, Jack M.

AU - Hattersley, Andrew T.

AU - Hu, Frank B.

AU - Jarvelin, Marjo Riitta

AU - Laakso, Markku

AU - Mooser, Vincent

AU - Ong, Ken K.

AU - Ouwehand, Willem H.

AU - Salomaa, Veikko

AU - Samani, Nilesh J.

AU - Spector, Timothy D.

AU - Tuomi, Tiinamaija

AU - Tuomilehto, Jaakko

AU - Uda, Manuela

AU - Uitterlinden, André G.

AU - Wareham, Nicholas J.

AU - Deloukas, Panagiotis

AU - Frayling, Timothy M.

AU - Groop, Leif C.

AU - Hayes, Richard B.

AU - Hunter, David J.

AU - Mohlke, Karen L.

AU - Peltonen, Leena

AU - Schlessinger, David

AU - Strachan, David P.

AU - Wichmann, H. Erich

AU - McCarthy, Mark I.

AU - Boehnke, Michael

AU - Barroso, Inês

AU - Abecasis, Gonçalo R.

AU - Hirschhorn, Joel N.

N1 - Funding Information: We are extremely grateful to all of the participants in each of the studies contributing to this effort. Full acknowledgments can be found in the Supplementary Note. Support for this research was provided by: US National Institutes of Health grants CA65725, CA87969, CA49449, CA67262, CA50385, DK062370, DK072193, DK075787, HG02651, HL084729, HL087679 (through STAMPEED, 1RL1MH083268), 5UO1CA098233, 1Z01 HG000024, 1RL1MH083268, T32 DK07191, F32 DK079466, K23 DK080145, K23 DK067288, CIDR NIH Contract Number N01-HG-65403, NIA contract NO1-AG-1-2109; the Intramural Research Program of the Division of Cancer Epidemiology and Genetics; contracts from the Division of Cancer Prevention, National Cancer Institute and EU FP6 funding (contract no LSHM-CT-2003-503041); GlaxoSmithKline; the Faculty of Biology and Medicine of Lausanne, Switzerland; the Intramural Research Program of the National Institute on Aging (NIA); Cancer Research United Kingdom; the UK Medical Research Council (including grants G0000649, G0000934 and G0601261); the Wellcome Trust (including Strategic Award 076113, grants 068545/Z/02 and 076467/Z/05/Z); the NIHR through the Biomedical Research Centres at Oxford, King’s College London; Guys and St. Thomas’ Foundation Hospitals’ Trust; the British Heart Foundation (including grant FS/05/061/19501), European Community’s Seventh Framework Programme (ENGAGE:HEALTH-F4-2007-201413); Diabetes UK; Unilever Corporate Research; American Diabetes Association including a Smith Family Foundation Pinnacle Program Project Award #7-03-PPG-04R; the Academy of Finland (grants 118065 and 124243); National Genome Research Net Germany; Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; the Helmholtz Center Munich; the Sigrid Juselius Foundation; University of Bristol; Linné grant from Swedish Research Council; Wallenberg Foundation; Folkhälsan Research Foundation; University of Southampton; Netherlands Organisation of Scientific Research NWO (nr. 175.010.2005.011); Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Ministry of Education, Culture and Science; the Netherlands Ministry for Health, Welfare and Sports; the European Commision (DG XII) and the Municipality of Rotterdam. G.R.A. and K.L.M. are Pew Scholars for the Biomedical Sciences; A.L.E. is supported by a Sarnoff Cardiovascular Research Foundation Fellowship; C.M.L. is a Nuffield Department of Medicine Scientific Leadership Fellow; S.A.M. is supported by a Life Sciences Research Fellowship; M.K. is supported by the Finnish Cultural Foundation; N.J.S. holds a BHF Chair; M.N.W. is a Vandervell Foundation Research Fellow; C.J.W. is supported by an American Diabetes Association postdoctoral fellowship; and E.Z. is a Wellcome Trust-RD Fellow (grant number 079557).

PY - 2009/1

Y1 - 2009/1

N2 - Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 × 10-8): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

AB - Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 × 10-8): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

UR - http://www.scopus.com/inward/record.url?scp=58149163142&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149163142&partnerID=8YFLogxK

U2 - 10.1038/ng.287

DO - 10.1038/ng.287

M3 - Article

C2 - 19079261

AN - SCOPUS:58149163142

SN - 1061-4036

VL - 41

SP - 25

EP - 34

JO - Nature genetics

JF - Nature genetics

IS - 1

ER -

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

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