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Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

Author(s): C. M. Lindgren, I. M. Heid, J. C. Randall, C. Lamina, V. Steinthorsdottir, L. Qi, E. K. Speliotes, G. Thorleifsson, C. J. Willer, B. M. Herrera, A. U. Jackson, N. Lim, P. Scheet, N. Soranzo, N. Amin, Y. S. Aulchenko, J. C. Chambers, A. Drong, J. A. Luan, H. N. Lyon, F. Rivadeneira, S. Sanna, N. J. Timpson, M. C. Zillikens, J. H. Zhao, P. Almgren, S. Bandinelli, A. J. Bennett, R. N. Bergman, L. L. Bonnycastle, S. J. Bumpstead, S. J. Chanock, L. Cherkas, P. Chines, L. Coin, C. Cooper, G. Crawford, A. Doering, A. Dominiczak, A. S. F. Doney, S. Ebrahim, P. Elliott, M. R. Erdos, K. Estrada, L. Ferrucci, G. Fischer, N. G. Forouhi, C. Gieger, H. Grallert, C. J. Groves, S. Grundy, C. Guiducci, D. Hadley, A. Hamsten, A. S. Havulinna, A. Hofman, R. Holle, J. W. Holloway, T. Illig, B. Isomaa, L. C. Jacobs, K. Jameson, P. Jousilahti, F. Karpe, J. Kuusisto, J. Laitinen, G. M. Lathrop, D. A. Lawlor, M. Mangino, W. L. McArdle, T. Meitinger, M. A. Morken, A. P. Morris, P. Munroe, N. Narisu, A. Nordstrom, P. Nordstrom, B. A. Oostra, C. N. A. Palmer, F. Payne, J. F. Peden, I. Prokopenko, F. Renstrom, A. Ruokonen, V. Salomaa, M. S. Sandhu, L. J. Scott, A. Scuteri, K. Silander, K. J. Song, X. Yuan, H. M. Stringham, A. J. Swift, T. Tuomi, M. Uda, P. Vollenweider, G. Waeber, C. Wallace, G. B. Walters, M. N. Weedon, J. C. M. Witteman, C. L. Zhang, W. H. Zhang, M. J. Caulfield, F. S. Collins, G. D. Smith, I. N. M. Day, P. W. Franks, A. T. Hattersley, F. B. Hu, M. R. Jarvelin, A. Kong, J. S. Kooner, M. Laakso, E. Lakatta, V. Mooser, A. D. Morris, L. Peltonen, N. J. Samani, T. D. Spector, D. P. Strachan, T. Tanaka, J. Tuomilehto, A. G. Uitterlinden, C. M. van Duijn, N. J. Wareham, H. Watkins, D. M. Waterworth, M. Boehnke, P. Deloukas, L. Groop, D. J. Hunter, U. Thorsteinsdottir, D. Schlessinger, H. E. Wichmann, T. M. Frayling, G. R. Abecasis, J. N. Hirschhorn, R. J. F. Loos, K. Stefansson, K. L. Mohlke, I. S. Barroso, M. I. McCarthy, Consor Wellcome Trust Case Control, Procardis Consortia, Giant Consortium

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.

Full version: Available here

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ISBN: 1553-7390
Publication Year: 2009
Periodical: Plos Genetics
Periodical Number: 6
Volume: 5
Author Address: