Twelve loci associated with bone density in middle-aged and elderly Chinese: the Shanghai Changfeng Study

Abstract Context Previous genome-wide association studies (GWAS) of bone mineral density (BMD) were mainly conducted in Europeans. Objective To explore genetic variants that affect BMD and sex differences in Chinese population. Methods A total of 5428 middle-aged and elderly Chinese were included. Dual-energy Xray absorptiometry (DXA) was used to measure BMD at lumbar spine, total and specific sites of hip. Mixed linear model was used to analyze the associations between BMD and autosomal genetic variants, adjusting for age, age squared, sex, and women menopause (model 1); model 2 further adjusted for height and weight. GWAS of osteoporosis in Biobank Japan (BBJ) project was used for replication. The GWAMA software was used to detect statistical significance of sex differences of estimated effects. Gene annotation and pathway enrichment analysis were performed. Results Women lost BMD at earlier ages and faster than men. The two models identified a total of 12 loci that were associated with BMD at any site. SNPs rs72354346, rs2024219, rs1463093, rs10037512, and rs5880932 were successfully replicated in BBJ. Variations of rs79262027 G > A (VKORC1L1) and rs4795209 A > G (DDX52) were associated with BMD only in men, and rs1239055408 G > GA (KCNJ2) was associated with BMD only in women. Gene enrichment analysis showed that BMD in Chinese elderly population were mainly related with ossification, bone resorption, sex hormone, and kidney physiology. Conclusion The present GWAS identified 12 loci that were significantly associated with BMD at any site in Chinese population, and 3 of them showed sex differences in effects.