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Pleiotropic loci underlying bone mineral density and bone size identified by a bivariate genome-wide association analysis

Zhang H1,2Liu L1,2,3Ni JJ1,2Wei XT2,4Feng GJ2,4Yang XL1,2Xu Q2,4Zhang ZJ5Hai R5Tian Q6Shen H6Deng HW7,8Pei YF9,10Zhang L11,12.

Osteoporos Int. 2020 Apr 20. doi: 10.1007/s00198-020-05389-x. [Epub ahead of print]



Aiming to identify pleiotropic genomic loci for bone mineral density and bone size, we performed a bivariate GWAS in five discovery samples and replicated in two large-scale samples. We identified 2 novel loci at 2q37.1 and 6q26. Our findings provide insight into common genetic architecture underlying both traits.


Bone mineral density (BMD) and bone size (BS) are two important factors that contribute to the development of osteoporosis and osteoporotic fracture. Both BMD and BS are highly heritable and they are genetically correlated. In this study, we aim to identify pleiotropic loci associated with BMD and BS.


We conducted a bivariate genome-wide association (GWA) analysis of hip BMD and hip BS in 6180 participants from 5 samples, followed by in silico replication in the UK Biobank study of BMD (N = 426,824) and the deCODE study of BS (N = 28,954), respectively.


SNPs from 2 genomic loci were significant at the genome-wide significance (GWS) level (p lt; 5 × 10-8) in the discovery samples and were successfully replicated in the replication samples (2q37.1, lead SNP rs7575512, discovery p = 1.49 × 10-10, replication p = 0.05; 6q26, lead SNP rs1040724, discovery p = 1.95 × 10-8, replication p = 0.03). Functional annotations suggested functional relevance of the identified variants to bone development.


Our findings provide insight into the common genetic architecture underlying BMD and BS, and enhance our understanding of the potential mechanism of osteoporosis fracture.