Comprehensive Analysis of the Genetic and Epigenetic Mechanisms of Osteoporosis and Bone Mineral Density

Hui Dong; Wenyang Zhou; Pingping Wang; Enjun Zuo; Xiaoxia Ying; Songling Chai; Tao Fei; Laidi Jin; Chen Chen; Guowu Ma; Huiying Liu

doi:10.3389/fcell.2020.00194

Comprehensive Analysis of the Genetic and Epigenetic Mechanisms of Osteoporosis and Bone Mineral Density

Front Cell Dev Biol. 2020 Mar 25:8:194. doi: 10.3389/fcell.2020.00194. eCollection 2020.

Authors

Hui Dong^{1

2}, Wenyang Zhou³, Pingping Wang³, Enjun Zuo¹, Xiaoxia Ying¹, Songling Chai¹, Tao Fei¹, Laidi Jin¹, Chen Chen¹, Guowu Ma¹, Huiying Liu¹

Affiliations

¹ Department of Oral Prosthodontics, School of Stomatology, Dalian Medical University, Dalian, China.
² Department of Stomatology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
³ School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.

Abstract

Osteoporosis is a skeletal disorder characterized by a systemic impairment of bone mineral density (BMD). Genome-wide association studies (GWAS) have identified hundreds of susceptibility loci for osteoporosis and BMD. However, the vast majority of susceptibility loci are located in non-coding regions of the genome and provide limited information about the genetic mechanisms of osteoporosis. Herein we performed a comprehensive functional analysis to investigate the genetic and epigenetic mechanisms of osteoporosis and BMD. BMD and osteoporosis are found to share many common susceptibility loci, and the corresponding susceptibility genes are significantly enriched in bone-related biological pathways. The regulatory element enrichment analysis indicated that BMD and osteoporosis susceptibility loci are significantly enriched in 5'UTR and DNase I hypersensitive sites (DHSs) of peripheral blood immune cells. By integrating GWAS and expression Quantitative Trait Locus (eQTL) data, we found that 15 protein-coding genes are regulated by the osteoporosis and BMD susceptibility loci. Our analysis provides new clues for a better understanding of the pathogenic mechanisms and offers potential therapeutic targets for osteoporosis.

Keywords: bone mineral density; functional element enrichment analysis; genome-wide association study; osteoporosis; summary data-based Mendelian randomization.