Identification of New Genes and Loci Associated With Bone Mineral Density Based on Mendelian Randomization

Abstract

Bone mineral density (BMD) is a complex and highly hereditary trait that can lead to osteoporotic fractures. It is estimated that BMD is mainly affected by genetic factors (about 85%). BMD has been reported to be associated with both common and rare variants, and numerous loci related to BMD have been identified by genome-wide association studies (GWAS). We systematically integrated expression quantitative trait loci (eQTL) data with GWAS summary statistical data. We mainly focused on the loci, which can affect gene expression, so Summary data-based Mendelian randomization (SMR) analysis was implemented to investigate new genes and loci associated with BMD. We identified 12,477 single-nucleotide polymorphisms (SNPs) regulating 564 genes, which are associated with BMD. The genetic mechanism we detected could make a contribution in the density of BMD in individuals and play an important role in understanding the pathophysiology of cataclasis.