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.

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