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

Lindgren, CM; Heid, IM; Randall, JC; Lamina, C; Steinthorsdottir, V; Qi, L; Speliotes, EK; Thorleifsson, G; Willer, CJ; Herrera, BM; +136 more...Jackson, AU; Lim, N; Scheet, P; Soranzo, N; Amin, N; Aulchenko, YS; Chambers, JC; Drong, A; Luan, J; Lyon, HN; Rivadeneira, F; Sanna, S; Timpson, NJ; Zillikens, MC; Zhao, JH; 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, AS; 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, CN; 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; Wellcome Trust Case Control Consortium; Witteman, JC; Zhang, C; Zhang, W; Caulfield, MJ; Collins, FS; Davey Smith, G; Day, IN; Franks, PW; Hattersley, AT; Hu, FB; Jarvelin, M; 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; Hugh Watkins; Procardis Consortia; Waterworth, DM; Boehnke, M; Deloukas, P; Groop, L; Hunter, DJ; Thorsteinsdottir, U; Schlessinger, D; Wichmann, H; Frayling, TM; Abecasis, GR; Hirschhorn, JN; Loos, RJ; Stefansson, K; Mohlke, KL; Barroso, I; McCarthy, MI; Giant Consortium and (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.