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

被引：9

作者：

Dong, Hui ^{[1
,2
]}

Zhou, Wenyang ^{[3
]}

Wang, Pingping ^{[3
]}

Zuo, Enjun ^{[1
]}

Ying, Xiaoxia ^{[1
]}

Chai, Songling ^{[1
]}

Fei, Tao ^{[1
]}

Jin, Laidi ^{[1
]}

Chen, Chen ^{[1
]}

Ma, Guowu ^{[1
]}

Liu, Huiying ^{[1
]}

机构：

[1] Dalian Med Univ, Sch Stomatol, Dept Oral Prosthodont, Dalian, Peoples R China

[2] Dalian Med Univ, Affiliated Hosp 1, Dept Stomatol, Dalian, Peoples R China

[3] Harbin Inst Technol, Sch Life Sci & Technol, Harbin, Peoples R China

来源：

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2020年 / 8卷

基金：

中国国家自然科学基金;

关键词：

genome-wide association study; osteoporosis; bone mineral density; summary data-based Mendelian randomization; functional element enrichment analysis; GENOME-WIDE ASSOCIATION; LOCI; GWAS; IDENTIFICATION; METAANALYSIS; INTEGRATION; MASS; EQTL; BMD;

D O I：

10.3389/fcell.2020.00194

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：8

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