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

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 asso...

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Detalles Bibliográficos
Autores principales: Lindgren, Cecilia M., Heid, Iris M., Randall, Joshua C., Lamina, Claudia, Steinthorsdottir, Valgerdur, Qi, Lu, Speliotes, Elizabeth K., Thorleifsson, Gudmar, Willer, Cristen J., Herrera, Blanca M., Jackson, Anne U., Lim, Noha, Scheet, Paul, Soranzo, Nicole, Amin, Najaf, Aulchenko, Yurii S., Chambers, John C., Drong, Alexander, Luan, Jian'an, Lyon, Helen N., Rivadeneira, Fernando, Sanna, Serena, Timpson, Nicholas J., Zillikens, M. Carola, Zhao, Jing Hua, Almgren, Peter, Bandinelli, Stefania, Bennett, Amanda J., Bergman, Richard N., Bonnycastle, Lori L., Bumpstead, Suzannah J., Chanock, Stephen J., Cherkas, Lynn, Chines, Peter, Coin, Lachlan, Cooper, Cyrus, Crawford, Gabriel, Doering, Angela, Dominiczak, Anna, Doney, Alex S. F., Ebrahim, Shah, Elliott, Paul, Erdos, Michael R., Estrada, Karol, Ferrucci, Luigi, Fischer, Guido, Forouhi, Nita G., Gieger, Christian, Grallert, Harald, Groves, Christopher J., Grundy, Scott, Guiducci, Candace, Hadley, David, Hamsten, Anders, Havulinna, Aki S., Hofman, Albert, Holle, Rolf, Holloway, John W., Illig, Thomas, Isomaa, Bo, Jacobs, Leonie C., Jameson, Karen, Jousilahti, Pekka, Karpe, Fredrik, Kuusisto, Johanna, Laitinen, Jaana, Lathrop, G. Mark, Lawlor, Debbie A., Mangino, Massimo, McArdle, Wendy L., Meitinger, Thomas, Morken, Mario A., Morris, Andrew P., Munroe, Patricia, Narisu, Narisu, Nordström, Anna, Nordström, Peter, Oostra, Ben A., Palmer, Colin N. A., Payne, Felicity, Peden, John F., Prokopenko, Inga, Renström, Frida, Ruokonen, Aimo, Salomaa, Veikko, Sandhu, Manjinder S., Scott, Laura J., Scuteri, Angelo, Silander, Kaisa, Song, Kijoung, Yuan, Xin, Stringham, Heather M., Swift, Amy J., Tuomi, Tiinamaija, Uda, Manuela, Vollenweider, Peter, Waeber, Gerard, Wallace, Chris, Walters, G. Bragi, Weedon, Michael N., Witteman, Jacqueline C. M., Zhang, Cuilin, Zhang, Weihua, Caulfield, Mark J., Collins, Francis S., Davey Smith, George, Day, Ian N. M., Franks, Paul W., Hattersley, Andrew T., Hu, Frank B., Jarvelin, Marjo-Riitta, Kong, Augustine, Kooner, Jaspal S., Laakso, Markku, Lakatta, Edward, Mooser, Vincent, Morris, Andrew D., Peltonen, Leena, Samani, Nilesh J., Spector, Timothy D., Strachan, David P., Tanaka, Toshiko, Tuomilehto, Jaakko, Uitterlinden, André G., van Duijn, Cornelia M., Wareham, Nicholas J., Watkins for the PROCARDIS consortia, Hugh, Waterworth, Dawn M., Boehnke, Michael, Deloukas, Panos, Groop, Leif, Hunter, David J., Thorsteinsdottir, Unnur, Schlessinger, David, Wichmann, H.-Erich, Frayling, Timothy M., Abecasis, Gonçalo R., Hirschhorn, Joel N., Loos, Ruth J. F., Stefansson, Kari, Mohlke, Karen L., Barroso, Inês, McCarthy for the GIANT consortium, Mark I.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695778/
https://www.ncbi.nlm.nih.gov/pubmed/19557161
http://dx.doi.org/10.1371/journal.pgen.1000508
Descripción
Sumario: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 = 1.9×10(−11)) and MSRA (WC, P = 8.9×10(−9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10(−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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