Genome-Wide Association Study of Bone Mineral Density in Premenopausal European-American Women and Replication in African-American Women

摘要

Context: Several genome-wide association studies (GWAS) have been performed to identify genes contributing to bone mineral density (BMD), typically in samples of elderly women and men.Objective: The objective of the study was to identify genes contributing to BMD in premenopausal women.Design: GWAS using the Illumina 610Quad array in premenopausal European-American (EA) women and replication of the top 50 single-nucleotide polymorphisms (SNPs) for two BMD measures in African-American (AA) women.Subjects: Subjects included 1524 premenopausal EA women aged 20–45 yr from 762 sibships and 669 AA premenopausal women aged 20–44 yr from 383 sibships.Interventions: There were no interventions.Main Outcome Measures: BMD was measured at the lumbar spine and femoral neck by dual-energy x-ray absorptiometry. Age- and weight-adjusted BMD values were tested for association with each SNP, with P values determined by permutation.Results: SNPs in CATSPERB on chromosome 14 provided evidence of association with femoral neck BMD (rs1298989, P = 2.7 × 10~(?5); rs1285635, P = 3.0 × 10~(?5)) in the EA women, and some supporting evidence was also observed with these SNPs in the AA women (rs1285635, P = 0.003). Genes identified in other BMD GWAS studies, including IBSP and ADAMTS18 , were also among the most significant findings in our GWAS.Conclusions: Evidence of association to several novel loci was detected in a GWAS of premenopausal EA women, and SNPs in one of these loci also provided supporting evidence in a sample of AA women.