Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution
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Date
2009
Author(s)
Lindgren, Cecilia M.
Heid, Iris M.
Randall, Joshua C.
Lamina, Claudia
Steinthorsdottir, Valgerdur
Speliotes, Elizabeth K.
Thorleifsson, Gudmar
Willer, Cristen J.
Herrera, Blanca M.
Jackson, Anne U.
Lim, Noha
Scheet, Paul
Soranzo, Nicole
Amin, Najaf
Aulchenko, Yurii S.
Chambers, John C.
Drong, Alexander
Luan, Jian'an
Rivadeneira, Fernando
Sanna, Serena
Timpson, Nicholas J.
Zillikens, M. Carola
Almgren, Peter
Bandinelli, Stefania
Bennett, Amanda J.
Bergman, Richard N.
Bonnycastle, Lori L.
Bumpstead, Suzannah J.
Chanock, Stephen J.
Cherkas, Lynn
Chines, Peter
Coin, Lachlan
Cooper, Cyrus
Crawford, Gabriel
Doering, Angela
Dominiczak, Anna
Doney, Alex S. F.
Ebrahim, Shah
Elliott, Paul
Erdos, Michael R.
Estrada, Karol
Ferrucci, Luigi
Fischer, Guido
Forouhi, Nita G.
Gieger, Christian
Grallert, Harald
Groves, Christopher J.
Grundy, Scott
Guiducci, Candace
Hadley, David
Hamsten, Anders
Havulinna, Aki S.
Holle, Rolf
Holloway, John W.
Illig, Thomas
Isomaa, Bo
Jacobs, Leonie C.
Jameson, Karen
Jousilahti, Pekka
Karpe, Fredrik
Kuusisto, Johanna
Laitinen, Jaana
Lathrop, G. Mark
Lawlor, Debbie A.
Mangino, Massimo
McArdle, Wendy L.
Meitinger, Thomas
Morken, Mario A.
Morris, Andrew P.
Munroe, Patricia
Narisu, Narisu
Nordström, Anna
Nordström, Peter
Oostra, Ben A.
Palmer, Colin N. A.
Payne, Felicity
Peden, John F.
Prokopenko, Inga
Renström, Frida
Ruokonen, Aimo
Salomaa, Veikko
Sandhu, Manjinder S.
Scuteri, Angelo
Silander, Kaisa
Song, Kijoung
Stringham, Heather M.
Swift, Amy J.
Tuomi, Tiinamaija
Uda, Manuela
Vollenweider, Peter
Waeber, Gerard
Wallace, Chris
Walters, G. Bragi
Weedon, Michael N.
Witteman, Jacqueline C. M.
Zhang, Cuilin
Zhang, Weihua
Caulfield, Mark J.
Collins, Francis S.
Davey Smith, George
Day, Ian N. M.
Franks, Paul W.
Hattersley, Andrew T.
Jarvelin, Marjo-Riitta
Kong, Augustine
Kooner, Jaspal S.
Laakso, Markku
Lakatta, Edward
Mooser, Vincent
Morris, Andrew D.
Peltonen, Leena
Samani, Nilesh J.
Spector, Timothy D.
Strachan, David P.
Tanaka, Toshiko
Tuomilehto, Jaakko
Uitterlinden, André G.
van Duijn, Cornelia M.
Wareham, Nicholas J.
Waterworth, Dawn M.
Boehnke, Michael
Deloukas, Panos
Groop, Leif
Thorsteinsdottir, Unnur
Schlessinger, David
Wichmann, H.-Erich
Frayling, Timothy M.
Abecasis, Gonçalo R.
Loos, Ruth J. F.
Stefansson, Kari
Mohlke, Karen L.
Barroso, Inês
McCarthy, Mark I.
Watkins, Hugh
The Wellcome Trust Case Control Consortium
Yuan, Xin
Scott, Laura J.
Hofman, Albert
Zhao, Jing Hua
Publisher
Public Library of Science
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Citation
Lindgren, Cecilia M., Iris M. Heid, Joshua C. Randall, Claudia Lamina, Valgerdur Steinthorsdottir, Lu Qi, Elizabeth K. Speliotes, et al. 2009. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genetics 5(6): e1000508.
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×\(10^{-11}\)) 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.
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