期刊
NATURE GENETICS
卷 43, 期 8, 页码 753-U58出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.866
关键词
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资金
- Academy of Finland [10404, 124243, 129680, 129494, 141005, 213506]
- Agency for Health Care Policy Research [HS06516]
- Althingi (the Icelandic Parliament)
- American Heart Association [10SDG269004]
- AstraZeneca
- Baltimore Geriatric Research Education and Clinical Centers
- Biocentrum Helsinki Foundation
- Biotechnology and Biological Sciences Research Council [G20234]
- British Heart Foundation [PG/07/133/24260, RG/08/008, SP/04/002, SP/07/007/23671]
- CamStrad
- Cancer Research UK
- Cedars-Sinai Board of Governors' Chair in Medical Genetics
- Centre for Medical Systems Biology (The Netherlands)
- Centre Hospitalier Universitaire Vaudois (Lausanne)
- Croatian Ministry of Science, Education and Sport [196-1962766-2747, 216-1080315-0302, 309-0061194-2023]
- Department of Health (UK)
- Department of Veterans Affairs (USA)
- Emil and Vera Cornell Foundation
- Erasmus Medical Center (Rotterdam)
- Erasmus University (Rotterdam)
- European Commission [FP7/2007-2013, FP7-KBBE-2010-4-266408, HEALTH-F2-2007-201681, HEALTH-F2-2008-201865-GEFOS, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550, LSHG-CT-2006-018947, LSHG-CT-2006-01947, LSHM-CT-2003-503041, LSHM-CT-2004-512013, QLG1-CT-2001-01252, QLG2-CT-2002-01254]
- Finnish Diabetes Foundation
- Finnish Diabetes Research Foundation
- Finnish Foundation for Cardiovascular Research
- Finnish Heart Foundation
- Finnish Medical Society
- Folkhalsan Research Foundation
- Food Standards Agency (UK)
- Foundation for Life and Health in Finland
- German Bundesministerium fur Forschung und Technology [01AK803A-H, 01IG07015G]
- German Federal Ministry of Education and Research
- German National Genome Research Network [NGFN-2, NGFNPlus: 01GS0823]
- Giorgi-Cavaglieri Foundation
- GlaxoSmithKline
- Goteborg Medical Society
- Gyllenberg Foundation
- Health and Safety Executive (UK)
- Health Care Center in Vasa
- Health Care Center in Narpes
- Health Care Center in Korsholm
- Hjartavernd (the Icelandic Heart Association)
- John D. and Catherine T. MacArthur Foundation
- Knut and Alice Wallenberg Foundation
- Leenaards Foundation
- Ludwig-Maximilians Universitat Munchen
- Lundberg Foundation
- Medical Research Council (UK)
- Men's Associates of Hebrew SeniorLife
- Ministerio de Ciencia e Innovacion (Spain) [SAF-2009, SAF-2008-02073]
- Ministry for Health, Welfare and Sports (The Netherlands)
- Ministry of Education (Finland)
- Ministry of Education, Culture and Science (The Netherlands)
- Municipal Health Care Center and Hospital in Jakobstad
- Municipality of Rotterdam
- Narpes Health Care Foundation
- National Institute for Health Research (UK)
- Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging [050-060-810]
- Netherlands Organisation for Scientific Research [175.010.2005.011, 911-03-012]
- Netherlands Organization for the Health Research and Development
- Nordic Center of Excellence in Disease Genetics
- Novo Nordisk Foundation
- Ollqvist Foundation
- Paavo Nurmi Foundation
- Perklen Foundation
- Petrus and Augusta Hedlunds Foundation
- Research Institute for Diseases in the Elderly [014-93-015, RIDE2]
- Robert Dawson Evans Endowment
- Royal Society (UK)
- Sahlgrenska Center for Cardiovascular and Metabolic Research [A305:188]
- Sahlgrenska University Hospital Foundation (ALF/LUA)
- Science Funding programme (UK)
- Scottish Executive Health Department
- Sigrid Juselius Foundation
- State of Bavaria
- Stroke Association (UK)
- Swedish Cultural Foundation in Finland
- Swedish Foundation for Strategic Research
- Swedish Research Council [K2010-54X-09894-19-3, K2010-52X-20229-05-3, 2006-3832]
- Swedish Strategic Foundation
- Swiss Institute of Bioinformatics
- Swiss National Science Foundation [3100AO-116323/1, 310000-112552, 33CSCO-122661]
- TEKES [1510/31/06]
- Torsten and Ragnar Soderberg's Foundation
- United Kingdom NIHR Cambridge Biomedical Research Centre
- University of Lausanne
- University of Maryland General Clinical Research Center [M01 RR 16500]
- Uppsala University
- MRC [G0601966, MC_U127561128, G0700931, G0701863, G0902037, G0802051, MC_U106188470] Funding Source: UKRI
- Academy of Finland (AKA) [141005, 141005] Funding Source: Academy of Finland (AKA)
- British Heart Foundation [RG/07/008/23674, SP/07/007/23671, RG/08/008/25291] Funding Source: researchfish
- Chief Scientist Office [CZB/4/710] Funding Source: researchfish
- Medical Research Council [G0100222, MC_U127561128, MC_U106179471, MC_U106188470, G0802051, G0601966, G0701863, G8802774, G0401527, G1000143, G0600717B, G0700931, G19/35, G0902037] Funding Source: researchfish
Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between similar to 2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 x 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 x 10(-11)) and one near SPRY2 (P = 3 x 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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