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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2010
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| Online Access: | http://hdl.handle.net/1721.1/52570 |
| _version_ | 1826188440941625344 |
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| author | Hunter, David J. Peltonen, Leena Guiducci, Candace Crawford, Gabriel Hirschhorn, Joel N. Lyon, Helen N. Speliotes, Elizabeth K. |
| author2 | Broad Institute of MIT and Harvard |
| author_facet | Broad Institute of MIT and Harvard Hunter, David J. Peltonen, Leena Guiducci, Candace Crawford, Gabriel Hirschhorn, Joel N. Lyon, Helen N. Speliotes, Elizabeth K. |
| author_sort | Hunter, David J. |
| collection | MIT |
| description | 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[superscript −11]) and MSRA (WC, P = 8.9×10[superscript −9]). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10[superscript −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. |
| first_indexed | 2024-09-23T07:59:41Z |
| format | Article |
| id | mit-1721.1/52570 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T07:59:41Z |
| publishDate | 2010 |
| publisher | Public Library of Science |
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| spelling | mit-1721.1/525702022-09-30T01:34:24Z Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution Hunter, David J. Peltonen, Leena Guiducci, Candace Crawford, Gabriel Hirschhorn, Joel N. Lyon, Helen N. Speliotes, Elizabeth K. Broad Institute of MIT and Harvard Peltonen, Leena Hunter, David J. Peltonen, Leena Guiducci, Candace Crawford, Gabriel Hirschhorn, Joel N. Lyon, Helen N. Speliotes, Elizabeth K. 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[superscript −11]) and MSRA (WC, P = 8.9×10[superscript −9]). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10[superscript −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. Vandervell Foundation and Wellcome Trust (068545/Z/02, GR072960, GR076113, GR069224, 086596/Z/08/Z) University of Oxford UK Department of Health Policy Research Programme UK National Institute of Health Research Swedish Medical Research Council (8691) Swedish Heart-Lung Foundation Support for Science Funding (UK) Stockholm County Council (560183) Scottish Executive Chief Scientist's Office Peninsula Medical School Novartis Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) (050-060-810) Netherlands Center of Medical Systems Biology Netherlands Organization for Scientific Research National Human Genome Research Institute (HG02651) National Institute of Diabetes and Digestive and Kidney Diseases (DK062370; DK072193; DK075787; DK079466; DK080145; DK067288; DK07191) National Heart, Lung and Blood Institute (HL087679 [STAMPEED], HL084729) National Institute on Aging National Institutes of Health (US: intramural programs (1Z01-HG000024) Munich Center of Health Sciences MedStar Research Institute Medical Research Council UK (G0000934, G0000649, G0601261, G0500539, G9521010D, G0600705) Knut and Alice Wallenberg Foundation Kings College London Karolinska Institute Sigrid Juselius Foundation GlaxoSmithKline German National Genome Research Net Folkhälsan Research Foundation Finnish Cultural Foundation Finnish Heart Association Swiss National Science Foundation (Grant 33CSCO-122661) Faculty of Biology and Medicine of Lausanne, Switzerland 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]) Diabetes UK Cancer Research UK, CIDR (NIH Contract Number N01-HG-65403) Camstrad British Heart Foundation Biotechnology and Biological Sciences Research Council (UK) Biocentrum Helsinki The Barts and The London Charity AstraZeneca AB Arthritis Research Campaign American Diabetes Association ADA Smith Family Foundation Pinnacle Program Academy of Finland (104781, 124243) 2010-03-15T13:12:35Z 2010-03-15T13:12:35Z 2009-06 2009-02 Article http://purl.org/eprint/type/JournalArticle 1553-7404 1553-7390 http://hdl.handle.net/1721.1/52570 Lindgren, Cecilia M. et al. “Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution.” PLoS Genet 5.6 (2009): e1000508. 19557161 en_US http://dx.doi.org/10.1371/journal.pgen.1000508 PLoS Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Hunter, David J. Peltonen, Leena Guiducci, Candace Crawford, Gabriel Hirschhorn, Joel N. Lyon, Helen N. Speliotes, Elizabeth K. Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution |
| title | Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution |
| title_full | Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution |
| title_fullStr | Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution |
| title_full_unstemmed | Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution |
| title_short | Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution |
| title_sort | genome wide association scan meta analysis identifies three loci influencing adiposity and fat distribution |
| url | http://hdl.handle.net/1721.1/52570 |
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