期刊
NATURE GENETICS
卷 44, 期 5, 页码 491-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2249
关键词
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资金
- European Commission [HEALTH-F2-2008-201865-GEFOS, QLRT-2001-02629]
- US National Institutes of Health (NIH) [R01 AG18728, R01 HL088119, R01AR046838, U01 HL084756, P30 DK072488, T32 AG000262, F32 AR059469, P01 AG-18397, R01 AG041517, M01 RR-00750, N01-AG-12100]
- NIA [AG-023629, AG-15928, AG-20098, AG-027058]
- Hjartavernd (the Icelandic Heart Association)
- Althingi (the Icelandic Parliament)
- Australian National Health and Medical Research Council [511132, 569807]
- Australian Cancer Research Foundation
- Rebecca Cooper Foundation
- MRC [MRC G0800582, 254627, 303169, 572604]
- Health Research Council of New Zealand
- Sanofi-Aventis
- Eli Lilly
- Pfizer
- Proctor & Gamble Pharmaceuticals
- Roche
- Living Well Foundation
- Ernst Heine Family Foundation
- Arthritis Research UK [17539, 15389]
- Victorian Health Promotion Foundation
- Geelong Region Medical Research Foundation, Australia [628582]
- Action Research UK
- UK Food Standards Agency
- BioPersMed [825329]
- Austrian Federal Ministry of Transport, Innovation and Technology (BMVIT)
- Austrian Federal Ministry of Economics and Labour (BMWA)
- Austrian Federal Ministry of Economy, Family and Youth (BMWFJ)
- Styrian Business Promotion Agency (SFG)
- Red de Envejecimiento y Fragilidad (RETICEF)
- Instituto Carlos III
- Spanish Ministry of Education and Science [SAF2010-15707]
- Government of Catalonia [2009SGR971, 2009SGR818]
- Instituto de Salud Carlos III-Fondo de Investigaciones Sanitarias [PI 06/0034, PI08/0183]
- Healthway Health Promotion Foundation of Western Australia
- Australasian Menopause Society
- Australian National Health
- Merck Frosst Canada
- Eli Lilly Canada
- Novartis Pharmaceuticals
- Procter & Gamble Pharmaceuticals Canada
- Servier Canada
- Amgen Canada
- Dairy Farmers of Canada
- Arthritis Society
- US National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL080295, HL075366, HL087652, HL105756 NINDS, HL 043851, HL69757, CA 047988]
- Framingham Heart Study [N01-HC-25195]
- Affymetrix, Inc, for genotyping services [N02-HL-6-4278]
- Eli Lilly International
- Amgen
- GE-Lunar
- Merck Australia
- Sanofi-Aventis Australia
- Servier
- US National Center for Research Resources [M01-RR00425]
- US National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]
- deCODE Genetics
- UK National Institute for Medical Research (NIMR) Biomedical Research Centre
- Cancer Research Campaign
- Stroke Association
- British Heart Foundation
- UK Department of Health
- Europe Against Cancer Programme Commission of the European Union
- Ministry of Agriculture, Fisheries and Food, EU Biomed 1 [BMHICT920182, CIPDCT925012, ERBC1PDCT 940229, ERBC1PDCT930105]
- UK MRC [G9321536, G9800062]
- Wellcome Trust Collaborative Research Initiative
- MAFF [AN0523]
- EU [QLK6-CT-2002-02629, LSHG-CT-2006-018947, HEALTH-F2-2009-223004 PHASE]
- Food Standards Agency [N05046]
- Netherlands Organization for Scientific Research (NWO)
- Erasmus University Medical Center
- Centre for Medical Systems Biology of the Netherlands Genomics Initiative (NGI) [CMSB1, CMSB2]
- F.I.R.M.O. Fondazione Raffaella Becagli
- National Institute on Aging [R01 AR/AG 41398, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098, R01 AR 050066]
- Canadian Institutes for Health Research [86748]
- Ministry of Education and Science of the Russian Federation Scientific and Pedagogical Staff of Innovative Russia [P-601]
- Federal Program Research and Development of Prior Directions of Scientific-Technological Complex of Russia [16.512.11.2032]
- Swedish Research Council [K2010-54X-09894-19-3, 2006-3832, K2010-52X-20229-05-3, K20006-72X-20155013]
- Swedish Foundation for Strategic Research
- ALF/LUA
- Lundberg Foundation
- Torsten and Ragnar Sderberg's Foundation
- Vastra Gotaland Foundation
- Goteborg Medical Society
- Novo Nordisk foundation, University of Athens, Greece
- UK NIHR Musculoskeletal BRU Oxford
- UK NIHR Nutrition BRU Southampton
- Center for Inherited Disease Research (CIDR)
- National Institutes of Health [HHSN268200782096C]
- Hong Kong Research Grant Council [HKU 768610M]
- HKU Foundation
- KC Wong Education Foundation [201007176237]
- Committee of Research and Conference Grants (CRCG)
- Osteoporosis and Endocrine Research Fund
- Genomics Strategic Research Theme of The University of Hong Kong
- Chinese University of Hong Kong
- Korea Health 21 Research & Development Project
- Korean Ministry of Health & Welfare, Republic of Korea [A010252]
- Korea Healthcare Technology Research & Development Project
- Ministry for Health, Welfare and Family Affairs [A110536]
- Netherlands Ministry of Health, Welfare and Sports Directorate of Long-Term Care
- World Anti-Doping Agency
- Danish Ministry of Culture
- Institute of Clinical Research of the University of Southern Denmark
- Chief Scientists Office of the Scottish Government [CZB/4/276]
- Royal Society
- Netherlands Organization of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]
- Research Institute for Diseases in the Elderly [RIDE2
- 014-93-015]
- Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging [01 IG 07015 G]
- NIHR Biomedical Research Centre
- Chronic Disease Research Foundation
- Canadian Institutes of Health Research
- Canadian Foundation for Innovation
- Fonds de la Recherche en Sante Quebec
- Lady Davis Institute
- Jewish General Hospital
- Ministere du Developpement Economique
- Swedish Sports Research Council [87/06]
- Swedish Society of Medicine
- Kempe Foundation [JCK-1021]
- Medical Faculty of Umea University [ALFVLL:968:22-2005, ALFVL:-937-2006, ALFVLL:223:11-2007, ALFVLL:78151-2009]
- County Council of Vasterbotten (Spjutspetsanslag) [VLL:159:33-2007]
- Donald W. Reynolds Foundation
- Fondation Leducq
- Academy of Finland [126925, 121584, 124282, 129378, 117787, 41071]
- Social Insurance Institution of Finland
- Tampere and Turku University
- Juho Vainio Foundation
- Paavo Nurmi Foundation
- Finnish Foundation of Cardiovascular Research
- Finnish Cultural Foundation
- Tampere Tuberculosis Foundation
- Emil Aaltonen Foundation [K08AR055688]
- MRC [G0800582, G9800062, MC_PC_U127561128, G0600705] Funding Source: UKRI
- British Heart Foundation [RG/08/014/24067] Funding Source: researchfish
- Chief Scientist Office [CZB/4/710] Funding Source: researchfish
- Medical Research Council [MC_U147585824, G0600705, MC_UP_A620_1014, G0401527, G9800062, MC_PC_U127561128, G1000143, U1475000001, G0800582] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10082] Funding Source: researchfish
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 x 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 x 10(-4), Bonferroni corrected), of which six reached P < 5 x 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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