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

Lindgren, C.M. et al. (2010) Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genetics, 6(4), e1000508. (doi: 10.1371/journal.pgen.1000508)

Abstract

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 = 2.66x10(-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

• Item Type: Articles
• Additional Information: This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
• Keywords: adiposity, adult obesity, association, cancer, common variants, diabetes, distribution, England, environmental- conditions, evolution, expression, fat, fat distribution, follow-up, fto gene, genetics, genome-wide association, Genome-Wide Association study, height, human, imputation, individuals, insulin-resistance, meta-analysis, metaanalysis, obesity, sequence variants, SNPS, variants, waist circumference, women
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dominiczak, Professor Anna
• Authors: Lindgren, C.M., Heid, I.M., Randall, J.C., Lamina, C., Steinthorsdottir, V., Qi, L., Speliotes, E.K., Thorleifsson, G., Willer, C.J., Herrera, B.M., Jackson, A.U., Lim, N., Scheet, P., Soranzo, N., Amin, N., Aulchenko, Y.S., Chambers, J.C., Drong, A., Luan, J.A., Lyon, H.N., Rivadeneira, F., Sanna, S., Timpson, N.J., Zillikens, M.C., Zhao, J.H., Almgren, P., Bandinelli, S., Bennett, A.J., Bergman, R.N., Bonnycastle, L.L., Bumpstead, S.J., Chanock, S.J., Cherkas, L., Chines, P., Coin, L., Cooper, C., Crawford, G., Doering, A., Dominiczak, A., Doney, A.S.F., Ebrahim, S., Elliott, P., Erdos, M.R., Estrada, K., Ferrucci, L., Fischer, G., Forouhi, N.G., Gieger, C., Grallert, H., Groves, C.J., Grundy, S., Guiducci, C., Hadley, D., Hamsten, A., Havulinna, A.S., Hofman, A., Holle, R., Holloway, J.W., Illig, T., Isomaa, B., Jacobs, L.C., Jameson, K., Jousilahti, P., Karpe, F., Kuusisto, J., Laitinen, J., Lathrop, G.M., Lawlor, D.A., Mangino, M., McArdle, W.L., Meitinger, T., Morken, M.A., Morris, A.P., Munroe, P., Narisu, N., Nordstrom, A., Nordstrom, P., Oostra, B.A., Palmer, C.N.A., Payne, F., Peden, J.F., Prokopenko, I., Renstrom, F., Ruokonen, A., Salomaa, V., Sandhu, M.S., Scott, L.J., Scuteri, A., Silander, K., Song, K., Yuan, X., Stringham, H.M., Swift, A.J., Tuomi, T., Uda, M., Vollenweider, P., Waeber, G., Wallace, C., Walters, G.B., Weedon, M.N., Witteman, J.C.M., Zhang, C.L., Zhang, W.H., Caulfield, M.J., Collins, F.S., Smith, G.D., Day, I.N.M., Franks, P.W., Hattersley, A.T., Hu, F.B., Jarvelin, M.R., Kong, A., Kooner, J.S., Laakso, M., Lakatta, E., Mooser, V., Morris, A.D., Peltonen, L., Samani, N.J., Spector, T.D., Strachan, D.P., Tanaka, T., Tuomilehto, J., Uitterlinden, A.G., van Duijn, C.M., Wareham, N.J., Waterworth, D.M., Boehnke, M., Deloukas, P., Groop, L., Hunter, D.J., Thorsteinsdottir, U., Schlessinger, D., Wichmann, H.E., Frayling, T.M., Abecasis, G.R., Hirschhorn, J.N., Loos, R.J.F., Stefansson, K., Mohlke, K.L., Barroso, I.S., and McCarthy, M.I.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: PLoS Genetics
• Publisher: Public Library of Science
• ISSN: 1553-7390
• ISSN (Online): 1553-7404
• Copyright Holders: Copyright © 2010 Lindgren et al.
• First Published: First published in PLoS Genetics 2010 6(4): e1000508
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher