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

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posted on 2012-10-24, 09:03 authored by 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, S. Grundy, M. R. Erdos, K. Estrada, L. Ferrucci, G. Fischer, N. G. Forouhi, C. Gieger, C. Guiducci, D. Hadley, A. Hamsten, G. Waeber, T. Illig, B. Isomaa, L. C. Jacobs, W. Zhang, K. Jameson, P. Jousilahti, F. Karpe, Wellcome Trust Case Control Consortium, J. Kuusisto, J. Laitinen, K. Silander, G. M. Lathrop, D. A. Lawlor, M. Mangino, W. L. McArdle, M. Uda, T. Meitinger, M. A. Morken, A. P. Morris, P. Munroe, J. C. Witteman, K. Song, N. Narisu, A. Nordström, P. Nordström, B. A. Oostra, C. N. Palmer, P. Vollenweider, F. Payne, J. F. Peden, I. Prokopenko, F. Renström, X. Yuan, A. Ruokonen, C. Zhang, V. Salomaa, M. S. Sandhu, L. J. Scott, A. Scuteri, H. M. Stringham, A. J. Swift, T. Tuomi, C. Wallace, G. B. Walters, M. N. Weedon, K. L. Mohlke, M. J. Caulfield, F. S. Collins, Davey Smith G., N. Amin, I. N. Day, P. W. Franks, A. T. Hattersley, N. Lim, F. B. Hu, M. R. Jarvelin, U. Thorsteinsdottir, A. Kong, J. S. Kooner, M. Laakso, E. Lakatta, R. J. Loos, V. Mooser, A. D. Morris, L. Peltonen, Nilesh J. Samani, P. Scheet, D. Schlessinger, T. D. Spector, D. P. Strachan, T. Tanaka, J. Tuomilehto, A. G. Uitterlinden, K. Stefansson, van Duijn C. M., N. J. Wareham, Watkins Hugh, Consortia Procardis, H. E. Wichmann, D. M. Waterworth, N. Soranzo, M. Boehnke, P. Deloukas, L. Groop, D. J. Hunter, T. M. Frayling, G. R. Abecasis, J. N. Hirschhorn, I. Barroso, M. I. McCarthy, Consortium Giant, J. W. Holloway, Y. S. Aulchenko, J. C. Chambers, A. Drong, A. S. Havulinna, J. Luan, H. N. Lyon, F. Rivadeneira, S. Sanna, N. J. Timpson, M. C. Zillikens, H. Grallert, J. H. Zhao, P. Almgren, S. Bandinelli, A. J. Bennett, A. Hofman, R. N. Bergman, L. L. Bonnycastle, S. J. Bumpstead, S. J. Chanock, L. Cherkas, C. J. Groves, P. Chines, L. Coin, C. Cooper, G. Crawford, A. Doering, R. Holle, A. Dominiczak, A. S. Doney, S. Ebrahim, P. Elliott
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.


Major project or personal funding for the work described in this paper comes from the Academy of Finland (104781, 124243), ADA Smith Family Foundation Pinnacle Program, the American Diabetes Association, Arthritis Research Campaign, AstraZeneca AB, The Barts and The London Charity, Biocentrum Helsinki, Biotechnology and Biological Sciences Research Council (UK), British Heart Foundation, Camstrad, Cancer Research UK, CIDR (NIH Contract Number N01-HG-65403), Diabetes UK, the European Commission (Framework VI: LSHG-CT-2004-518153 [EURODIA]; LSHG-CT-2004-512066 [MolPAGE]; LSHM-CT-2006-037197; LSHM-CT-2003-503041; QL46-CT-2002-02629 [GENOMOS]; LSHM-CT-2007-037273; Framework VII: HEALTH-F4-2007- 201413 [ENGAGE]), the Faculty of Biology and Medicine of Lausanne, Switzerland, the Swiss National Science Foundation (Grant 33CSCO-122661, the Finnish Heart Association, the Finnish Cultural Foundation, Folkhälsan Research Foundation, the German National Genome Research Net, GlaxoSmithKline, the Sigrid Juselius Foundation, the Karolinska Institute, Kings College London, the Knut and Alice Wallenberg Foundation, the Medical Research Council UK (G0000934, G0000649, G0601261, G0500539, G9521010D, G0600705), MedStar Research Institute, Munich Center of Health Sciences, National Institutes of Health (US: intramural programs (1Z01-HG000024), National Institute on Aging; NHLBI (HL087679 [STAMPEED], HL084729), NIDDK (DK062370; DK072193; DK075787; DK079466; DK080145; DK067288; DK07191), NHGRI (HG02651), the Netherlands Organization for Scientific Research, the Netherlands Center of Medical Systems Biology, the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) (050-060-810), Novartis, Peninsula Medical School, Scottish Executive Chief Scientist's Office, Stockholm County Council (560183), Support for Science Funding (UK); Swedish Heart-Lung Foundation, the Swedish Medical Research Council (8691), UK National Institute of Health Research, UK Depa



PLoS Genetics, 2009, 5 (6), pp. e1000508-e1000508

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