Joint study of two genome-wide association meta-analyses identified 20p12.1 and 20q13.33 for bone mineral density.

In the present study, aiming to identify loci associated with osteoporosis, we conducted a joint association study of 2 independent genome-wide association meta-analyses of femoral neck and lumbar spine bone mineral densities (BMDs): 1) an in-house study of 6 samples involving 7484 subjects, and 2) the GEFOS-seq study of 7 samples involving 32,965 subjects. The in-house samples were imputed by the 1000 genomes project phase 3 reference panel. SNP-based association test was applied to 7,998,108 autosomal SNPs in each meta-analysis, and for each SNP the 2 association signals were then combined for joint analysis and for mutual replication. Combining the evidence from both studies, we identified 2 novel loci associated with BMDs at the genome-wide significance level (α=5.0×10-8): 20p12.1 (rs73100693 p=2.65×10-8, closest gene MACROD2) and 20q13.33 (rs2380128 p=3.44×10-8, OSBPL2). We also replicated 7 loci that were reported by two recent studies on heel and total body BMD. Our findings provide useful insights that enhance our understanding of bone development, osteoporosis and fracture pathogenesis.

up to 4,692 European ancestry individuals, up to 1,539 Han Chinese ancestry individuals, up to 849 African American individuals, up to 446 Hispanic individuals, 2,882 European ancestry whole-genome sequenced individuals, 3,549 European ancestry whole-exome sequenced individuals, 26,534 European ancestry non-array genotype imputed individuals