Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies (original) (raw)

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 loci reaching genome-wide significance (GWS; P<5×10−8), of which 13 map to new regions including 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 metaanalysis 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 numerous SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism, and highlight the complex genetic architecture underlying osteoporosis and BMD variation.