Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

Cecilia M. Lindgren; Iris M. Heid; Joshua C. Randall; Claudia Lamina; Valgerdur Steinthorsdottir; Lu Qi; Elizabeth K. Speliotes; Gudmar Thorleifsson; Cristen J. Willer; Blanca M. Herrera; Anne U. Jackson; Noha Lim; Paul Scheet; Nicole Soranzo; Najaf Amin; Yurii S. Aulchenko; John C. Chambers; Alexander Drong; Jia N.an Luan; Helen N. Lyon; Fernando Rivadeneira; Serena Sanna; Nicholas J. Timpson; M. Carola Zillikens; Hua Zhao Jing; Peter Almgren; Stefania Bandinelli; Amanda J. Bennett; Richard N. Bergman; Lori L. Bonnycastle; Suzannah J. Bumpstead; Stephen J. Chanock; Lynn Cherkas; Peter Chines; Lachlan Coin; Cyrus Cooper; Gabriel Crawford; Angela Doering; Anna Dominiczak; Alex S.F. Doney; Shah Ebrahim; Paul Elliott; Michael R. Erdos; Karol Estrada; Luigi Ferrucci; Guido Fischer; Nita G. Forouhi; Christian Gieger; Harald Grallert; Christopher J. Groves; Scott Grundy; Candace Guiducci; David Hadley; Anders Hamsten; Aki S. Havulinna; Albert Hofman; Rolf Holle; John W. Holloway; Thomas Illig; Bo Isomaa; Leonie C. Jacobs; Karen Jameson; Pekka Jousilahti; Fredrik Karpe; Johanna Kuusisto; Jaana Laitinen; G. Mark Lathrop; Debbie A. Lawlor; Massimo Mangino; Wendy L. McArdle; Thomas Meitinger; Mario A. Morken; Andrew P. Morris; Patricia Munroe; Narisu Narisu; Anna Nordström; Peter Nordström; Ben A. Oostra; Colin N.A. Palmer; Felicity Payne; John F. Peden; Inga Prokopenko; Frida Renström; Aimo Ruokonen; Veikko Salomaa; Manjinder S. Sandhu; Laura J. Scott; Angelo Scuteri; Kaisa Silander; Kijoung Song; Xin Yuan; Heather M. Stringham; Amy J. Swift; Tiinamaija Tuomi; Manuela Uda; Peter Vollenweider; Gerard Waeber; Chris Wallace; G. Bragi Walters; Michael N. Weedon; Jacqueline C.M. Witteman; Cuilin Zhang; Weihua Zhang; Mark J. Caulfield; Francis S. Collins; George Davey Smith; Ian N.M. Day; Paul W. Franks; Andrew T. Hattersley; Frank B. Hu; Marjo Riitta Jarvelin; Augustine Kong; Jaspal S. Kooner; Markku Laakso; Edward Lakatta; Vincent Mooser; Andrew D. Morris; Leena Peltonen; Nilesh J. Samani; Timothy D. Spector; David P. Strachan; Toshiko Tanaka; Jaakko Tuomilehto; André G. Uitterlinden; Cornelia M. Van Duijn; Nicholas J. Wareham; Hugh Watkins; Dawn M. Waterworth; Michael Boehnke; Panos Deloukas; Leif Groop; David J. Hunter; Unnur Thorsteinsdottir; David Schlessinger; H. Erich Wichmann; Timothy M. Frayling; Gonçalo R. Abecasis; Joel N. Hirschhorn; Ruth J.F. Loos; Kari Stefansson; Karen L. Mohlke; Inês Barroso; Mark I. McCarthy

doi:10.1371/journal.pgen.1000508

Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

Cecilia M. Lindgren, Iris M. Heid, Joshua C. Randall, Claudia Lamina, Valgerdur Steinthorsdottir, Lu Qi, Elizabeth K. Speliotes, Gudmar Thorleifsson, Cristen J. Willer, Blanca M. Herrera, Anne U. Jackson, Noha Lim, Paul Scheet, Nicole Soranzo, Najaf Amin, Yurii S. Aulchenko, John C. Chambers, Alexander Drong, Jia N.an Luan, Helen N. LyonFernando Rivadeneira, Serena Sanna, Nicholas J. Timpson, M. Carola Zillikens, Hua Zhao Jing, Peter Almgren, Stefania Bandinelli, Amanda J. Bennett, Richard N. Bergman, Lori L. Bonnycastle, Suzannah J. Bumpstead, Stephen J. Chanock, Lynn Cherkas, Peter Chines, Lachlan Coin, Cyrus Cooper, Gabriel Crawford, Angela Doering, Anna Dominiczak, Alex S.F. Doney, Shah Ebrahim, Paul Elliott, Michael R. Erdos, Karol Estrada, Luigi Ferrucci, Guido Fischer, Nita G. Forouhi, Christian Gieger, Harald Grallert, Christopher J. Groves, Scott Grundy, Candace Guiducci, David Hadley, Anders Hamsten, Aki S. Havulinna, Albert Hofman, Rolf Holle, John W. Holloway, Thomas Illig, Bo Isomaa, Leonie C. Jacobs, Karen Jameson, Pekka Jousilahti, Fredrik Karpe, Johanna Kuusisto, Jaana Laitinen, G. Mark Lathrop, Debbie A. Lawlor, Massimo Mangino, Wendy L. McArdle, Thomas Meitinger, Mario A. Morken, Andrew P. Morris, Patricia Munroe, Narisu Narisu, Anna Nordström, Peter Nordström, Ben A. Oostra, Colin N.A. Palmer, Felicity Payne, John F. Peden, Inga Prokopenko, Frida Renström, Aimo Ruokonen, Veikko Salomaa, Manjinder S. Sandhu, Laura J. Scott, Angelo Scuteri, Kaisa Silander, Kijoung Song, Xin Yuan, Heather M. Stringham, Amy J. Swift, Tiinamaija Tuomi, Manuela Uda, Peter Vollenweider, Gerard Waeber, Chris Wallace, G. Bragi Walters, Michael N. Weedon, Jacqueline C.M. Witteman, Cuilin Zhang, Weihua Zhang, Mark J. Caulfield, Francis S. Collins, George Davey Smith, Ian N.M. Day, Paul W. Franks, Andrew T. Hattersley, Frank B. Hu, Marjo Riitta Jarvelin, Augustine Kong, Jaspal S. Kooner, Markku Laakso, Edward Lakatta, Vincent Mooser, Andrew D. Morris, Leena Peltonen, Nilesh J. Samani, Timothy D. Spector, David P. Strachan, Toshiko Tanaka, Jaakko Tuomilehto, André G. Uitterlinden, Cornelia M. Van Duijn, Nicholas J. Wareham, Hugh Watkins, Dawn M. Waterworth, Michael Boehnke, Panos Deloukas, Leif Groop, David J. Hunter, Unnur Thorsteinsdottir, David Schlessinger, H. Erich Wichmann, Timothy M. Frayling, Gonçalo R. Abecasis, Joel N. Hirschhorn, Ruth J.F. Loos, Kari Stefansson, Karen L. Mohlke, Inês Barroso, Mark I. McCarthy

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

440 Scopus citations

Abstract

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×102 ^-11) and MSRA (WC, P = 8.9×10^-9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10 ^-8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

Original language	English
Article number	e1000508
Journal	PLoS Genetics
Volume	5
Issue number	6
DOIs	https://doi.org/10.1371/journal.pgen.1000508
State	Published - Jun 2009
Externally published	Yes

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10.1371/journal.pgen.1000508

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Lindgren, C. M., Heid, I. M., Randall, J. C., Lamina, C., Steinthorsdottir, V., Qi, L., Speliotes, E. K., Thorleifsson, G., Willer, C. J., Herrera, B. M., Jackson, A. U., Lim, N., Scheet, P., Soranzo, N., Amin, N., Aulchenko, Y. S., Chambers, J. C., Drong, A., Luan, J. N. A., ... McCarthy, M. I. (2009). Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genetics, 5(6), Article e1000508. https://doi.org/10.1371/journal.pgen.1000508

@article{3dc2a0e46e914b2bbc2e86f07c406a9c,

title = "Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution",

abstract = "To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×102 -11) and MSRA (WC, P = 8.9×10-9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10 -8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.",

author = "Lindgren, {Cecilia M.} and Heid, {Iris M.} and Randall, {Joshua C.} and Claudia Lamina and Valgerdur Steinthorsdottir and Lu Qi and Speliotes, {Elizabeth K.} and Gudmar Thorleifsson and Willer, {Cristen J.} and Herrera, {Blanca M.} and Jackson, {Anne U.} and Noha Lim and Paul Scheet and Nicole Soranzo and Najaf Amin and Aulchenko, {Yurii S.} and Chambers, {John C.} and Alexander Drong and Luan, {Jia N.an} and Lyon, {Helen N.} and Fernando Rivadeneira and Serena Sanna and Timpson, {Nicholas J.} and Zillikens, {M. Carola} and Jing, {Hua Zhao} and Peter Almgren and Stefania Bandinelli and Bennett, {Amanda J.} and Bergman, {Richard N.} and Bonnycastle, {Lori L.} and Bumpstead, {Suzannah J.} and Chanock, {Stephen J.} and Lynn Cherkas and Peter Chines and Lachlan Coin and Cyrus Cooper and Gabriel Crawford and Angela Doering and Anna Dominiczak and Doney, {Alex S.F.} and Shah Ebrahim and Paul Elliott and Erdos, {Michael R.} and Karol Estrada and Luigi Ferrucci and Guido Fischer and Forouhi, {Nita G.} and Christian Gieger and Harald Grallert and Groves, {Christopher J.} and Scott Grundy and Candace Guiducci and David Hadley and Anders Hamsten and Havulinna, {Aki S.} and Albert Hofman and Rolf Holle and Holloway, {John W.} and Thomas Illig and Bo Isomaa and Jacobs, {Leonie C.} and Karen Jameson and Pekka Jousilahti and Fredrik Karpe and Johanna Kuusisto and Jaana Laitinen and Lathrop, {G. Mark} and Lawlor, {Debbie A.} and Massimo Mangino and McArdle, {Wendy L.} and Thomas Meitinger and Morken, {Mario A.} and Morris, {Andrew P.} and Patricia Munroe and Narisu Narisu and Anna Nordstr{\"o}m and Peter Nordstr{\"o}m and Oostra, {Ben A.} and Palmer, {Colin N.A.} and Felicity Payne and Peden, {John F.} and Inga Prokopenko and Frida Renstr{\"o}m and Aimo Ruokonen and Veikko Salomaa and Sandhu, {Manjinder S.} and Scott, {Laura J.} and Angelo Scuteri and Kaisa Silander and Kijoung Song and Xin Yuan and Stringham, {Heather M.} and Swift, {Amy J.} and Tiinamaija Tuomi and Manuela Uda and Peter Vollenweider and Gerard Waeber and Chris Wallace and Walters, {G. Bragi} and Weedon, {Michael N.} and Witteman, {Jacqueline C.M.} and Cuilin Zhang and Weihua Zhang and Caulfield, {Mark J.} and Collins, {Francis S.} and Smith, {George Davey} and Day, {Ian N.M.} and Franks, {Paul W.} and Hattersley, {Andrew T.} and Hu, {Frank B.} and Jarvelin, {Marjo Riitta} and Augustine Kong and Kooner, {Jaspal S.} and Markku Laakso and Edward Lakatta and Vincent Mooser and Morris, {Andrew D.} and Leena Peltonen and Samani, {Nilesh J.} and Spector, {Timothy D.} and Strachan, {David P.} and Toshiko Tanaka and Jaakko Tuomilehto and Uitterlinden, {Andr{\'e} G.} and {Van Duijn}, {Cornelia M.} and Wareham, {Nicholas J.} and Hugh Watkins and Waterworth, {Dawn M.} and Michael Boehnke and Panos Deloukas and Leif Groop and Hunter, {David J.} and Unnur Thorsteinsdottir and David Schlessinger and Wichmann, {H. Erich} and Frayling, {Timothy M.} and Abecasis, {Gon{\c c}alo R.} and Hirschhorn, {Joel N.} and Loos, {Ruth J.F.} and Kari Stefansson and Mohlke, {Karen L.} and In{\^e}s Barroso and McCarthy, {Mark I.}",

year = "2009",

month = jun,

doi = "10.1371/journal.pgen.1000508",

language = "English",

volume = "5",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "6",

}

Lindgren, CM, Heid, IM, Randall, JC, Lamina, C, Steinthorsdottir, V, Qi, L, Speliotes, EK, Thorleifsson, G, Willer, CJ, Herrera, BM, Jackson, AU, Lim, N, Scheet, P, Soranzo, N, Amin, N, Aulchenko, YS, Chambers, JC, Drong, A, Luan, JNA, Lyon, HN, Rivadeneira, F, Sanna, S, Timpson, NJ, Zillikens, MC, Jing, HZ, Almgren, P, Bandinelli, S, Bennett, AJ, Bergman, RN, Bonnycastle, LL, Bumpstead, SJ, Chanock, SJ, Cherkas, L, Chines, P, Coin, L, Cooper, C, Crawford, G, Doering, A, Dominiczak, A, Doney, ASF, Ebrahim, S, Elliott, P, Erdos, MR, Estrada, K, Ferrucci, L, Fischer, G, Forouhi, NG, Gieger, C, Grallert, H, Groves, CJ, Grundy, S, Guiducci, C, Hadley, D, Hamsten, A, Havulinna, AS, Hofman, A, Holle, R, Holloway, JW, Illig, T, Isomaa, B, Jacobs, LC, Jameson, K, Jousilahti, P, Karpe, F, Kuusisto, J, Laitinen, J, Lathrop, GM, Lawlor, DA, Mangino, M, McArdle, WL, Meitinger, T, Morken, MA, Morris, AP, Munroe, P, Narisu, N, Nordström, A, Nordström, P, Oostra, BA, Palmer, CNA, Payne, F, Peden, JF, Prokopenko, I, Renström, F, Ruokonen, A, Salomaa, V, Sandhu, MS, Scott, LJ, Scuteri, A, Silander, K, Song, K, Yuan, X, Stringham, HM, Swift, AJ, Tuomi, T, Uda, M, Vollenweider, P, Waeber, G, Wallace, C, Walters, GB, Weedon, MN, Witteman, JCM, Zhang, C, Zhang, W, Caulfield, MJ, Collins, FS, Smith, GD, Day, INM, Franks, PW, Hattersley, AT, Hu, FB, Jarvelin, MR, Kong, A, Kooner, JS, Laakso, M, Lakatta, E, Mooser, V, Morris, AD, Peltonen, L, Samani, NJ, Spector, TD, Strachan, DP, Tanaka, T, Tuomilehto, J, Uitterlinden, AG, Van Duijn, CM, Wareham, NJ, Watkins, H, Waterworth, DM, Boehnke, M, Deloukas, P, Groop, L, Hunter, DJ, Thorsteinsdottir, U, Schlessinger, D, Wichmann, HE, Frayling, TM, Abecasis, GR, Hirschhorn, JN, Loos, RJF, Stefansson, K, Mohlke, KL, Barroso, I & McCarthy, MI 2009, 'Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution', PLoS Genetics, vol. 5, no. 6, e1000508. https://doi.org/10.1371/journal.pgen.1000508

TY - JOUR

T1 - Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

AU - Lindgren, Cecilia M.

AU - Heid, Iris M.

AU - Randall, Joshua C.

AU - Lamina, Claudia

AU - Steinthorsdottir, Valgerdur

AU - Qi, Lu

AU - Speliotes, Elizabeth K.

AU - Thorleifsson, Gudmar

AU - Willer, Cristen J.

AU - Herrera, Blanca M.

AU - Jackson, Anne U.

AU - Lim, Noha

AU - Scheet, Paul

AU - Soranzo, Nicole

AU - Amin, Najaf

AU - Aulchenko, Yurii S.

AU - Chambers, John C.

AU - Drong, Alexander

AU - Luan, Jia N.an

AU - Lyon, Helen N.

AU - Rivadeneira, Fernando

AU - Sanna, Serena

AU - Timpson, Nicholas J.

AU - Zillikens, M. Carola

AU - Jing, Hua Zhao

AU - Almgren, Peter

AU - Bandinelli, Stefania

AU - Bennett, Amanda J.

AU - Bergman, Richard N.

AU - Bonnycastle, Lori L.

AU - Bumpstead, Suzannah J.

AU - Chanock, Stephen J.

AU - Cherkas, Lynn

AU - Chines, Peter

AU - Coin, Lachlan

AU - Cooper, Cyrus

AU - Crawford, Gabriel

AU - Doering, Angela

AU - Dominiczak, Anna

AU - Doney, Alex S.F.

AU - Ebrahim, Shah

AU - Elliott, Paul

AU - Erdos, Michael R.

AU - Estrada, Karol

AU - Ferrucci, Luigi

AU - Fischer, Guido

AU - Forouhi, Nita G.

AU - Gieger, Christian

AU - Grallert, Harald

AU - Groves, Christopher J.

AU - Grundy, Scott

AU - Guiducci, Candace

AU - Hadley, David

AU - Hamsten, Anders

AU - Havulinna, Aki S.

AU - Hofman, Albert

AU - Holle, Rolf

AU - Holloway, John W.

AU - Illig, Thomas

AU - Isomaa, Bo

AU - Jacobs, Leonie C.

AU - Jameson, Karen

AU - Jousilahti, Pekka

AU - Karpe, Fredrik

AU - Kuusisto, Johanna

AU - Laitinen, Jaana

AU - Lathrop, G. Mark

AU - Lawlor, Debbie A.

AU - Mangino, Massimo

AU - McArdle, Wendy L.

AU - Meitinger, Thomas

AU - Morken, Mario A.

AU - Morris, Andrew P.

AU - Munroe, Patricia

AU - Narisu, Narisu

AU - Nordström, Anna

AU - Nordström, Peter

AU - Oostra, Ben A.

AU - Palmer, Colin N.A.

AU - Payne, Felicity

AU - Peden, John F.

AU - Prokopenko, Inga

AU - Renström, Frida

AU - Ruokonen, Aimo

AU - Salomaa, Veikko

AU - Sandhu, Manjinder S.

AU - Scott, Laura J.

AU - Scuteri, Angelo

AU - Silander, Kaisa

AU - Song, Kijoung

AU - Yuan, Xin

AU - Stringham, Heather M.

AU - Swift, Amy J.

AU - Tuomi, Tiinamaija

AU - Uda, Manuela

AU - Vollenweider, Peter

AU - Waeber, Gerard

AU - Wallace, Chris

AU - Walters, G. Bragi

AU - Weedon, Michael N.

AU - Witteman, Jacqueline C.M.

AU - Zhang, Cuilin

AU - Zhang, Weihua

AU - Caulfield, Mark J.

AU - Collins, Francis S.

AU - Smith, George Davey

AU - Day, Ian N.M.

AU - Franks, Paul W.

AU - Hattersley, Andrew T.

AU - Hu, Frank B.

AU - Jarvelin, Marjo Riitta

AU - Kong, Augustine

AU - Kooner, Jaspal S.

AU - Laakso, Markku

AU - Lakatta, Edward

AU - Mooser, Vincent

AU - Morris, Andrew D.

AU - Peltonen, Leena

AU - Samani, Nilesh J.

AU - Spector, Timothy D.

AU - Strachan, David P.

AU - Tanaka, Toshiko

AU - Tuomilehto, Jaakko

AU - Uitterlinden, André G.

AU - Van Duijn, Cornelia M.

AU - Wareham, Nicholas J.

AU - Watkins, Hugh

AU - Waterworth, Dawn M.

AU - Boehnke, Michael

AU - Deloukas, Panos

AU - Groop, Leif

AU - Hunter, David J.

AU - Thorsteinsdottir, Unnur

AU - Schlessinger, David

AU - Wichmann, H. Erich

AU - Frayling, Timothy M.

AU - Abecasis, Gonçalo R.

AU - Hirschhorn, Joel N.

AU - Loos, Ruth J.F.

AU - Stefansson, Kari

AU - Mohlke, Karen L.

AU - Barroso, Inês

AU - McCarthy, Mark I.

PY - 2009/6

Y1 - 2009/6

N2 - To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×102 -11) and MSRA (WC, P = 8.9×10-9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10 -8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

AB - To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×102 -11) and MSRA (WC, P = 8.9×10-9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10 -8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

UR - http://www.scopus.com/inward/record.url?scp=67651236725&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1000508

DO - 10.1371/journal.pgen.1000508

M3 - Article

C2 - 19557161

AN - SCOPUS:67651236725

SN - 1553-7390

VL - 5

JO - PLoS Genetics

JF - PLoS Genetics

IS - 6

M1 - e1000508

ER -

Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

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