Journal
NATURE GENETICS
Volume 41, Issue 11, Pages 1199-U58Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.446
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Funding
- European Commission [HEALTH-F2-2008-201865GEFOS]
- Netherlands Organization of Scientific Research NWO Investments [175.010.2005.011, 91103-012]
- Research Institute for Diseases in the Elderly [014-93-015, RIDE2]
- Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) [050-060-810]
- Erasmus Medical Center and Erasmus University, Rotterdam
- Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
- Netherlands Organization for Scientific Research (NWO)
- Erasmus MC
- Centre for Medical Systems Biology (CMSB)
- Wellcome Trust
- Arthritis Research Campaign
- Chronic Disease Research Foundation
- Canadian Institutes of Health Research
- European Society for Clinical and Economic Aspects of Osteoporosis
- European Union FP-5 [QLG2-CT-2002-01254]
- National Institute for Health Research (NIHR)
- US National Institute for Arthritis, Musculoskeletal and Skin Diseases
- National Institute on Aging [R01 AR/AG 41398, R01 AR 050066]
- National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]
- Affymetrix, Inc. [N02-HL-6-4278]
- Genome Quebec
- Genome Canada
- Canadian Institutes of Health Research (CIHR)
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Bone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 1p31.3 (GPR177), 2p21 (SPTBN1), 3p22 (CTNNB1), 4q21.1 (MEPE), 5q14 (MEF2C), 7p14 (STARD3NL), 7q21.3 (FLJ42280), 11p11.2 (LRP4, ARHGAP1, F2), 11p14.1 (DCDC5), 11p15 (SOX6), 16q24 (FOXL1), 17q21 (HDAC5) and 17q12 (CRHR1). The meta-analysis also confirmed at GWS level seven known BMD loci on 1p36 (ZBTB40), 6q25 (ESR1), 8q24 (TNFRSF11B), 11q13.4 (LRP5), 12q13 (SP7), 13q14 (TNFSF11) and 18q21 (TNFRSF11A). The many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD.
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