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JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
Joint study of two genome-wide association meta-analyses identified 20p12.1 and 20q13.33 for bone mineral density.
Bone 2018 May
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.
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