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 ; +136 more... Anne U Jackson ; Noha Lim ; Paul Scheet ; Nicole Soranzo ; Najaf Amin ; Yurii S Aulchenko ; John C Chambers ; Alexander Drong ; Jian'an Luan ; Helen N Lyon ; Fernando Rivadeneira ; Serena Sanna ; Nicholas J Timpson ; M Carola Zillikens ; Jing Hua Zhao ; 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 SF 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 NA 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 ; Wellcome Trust Case Control Consortium ; Jacqueline CM Witteman ; Cuilin Zhang ; Weihua Zhang ; Mark J Caulfield ; Francis S Collins ; George Davey Smith ; Ian NM 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 ; Procardis Consortia ; 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 JF Loos ; Kari Stefansson ; Karen L Mohlke ; Inês Barroso ; Mark I McCarthy ; Giant Consortium ; (2009) Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution. PLoS genetics, 5 (6). e1000508-. ISSN 1553-7390 DOI: 10.1371/journal.pgen.1000508

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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 = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-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.