Comprehensive Analysis of the Genetic and Epigenetic Mechanisms of Osteoporosis and Bone Mineral Density
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 regio...
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00194/full |
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| author | Hui Dong Hui Dong Wenyang Zhou Pingping Wang Enjun Zuo Xiaoxia Ying Songling Chai Tao Fei Laidi Jin Chen Chen Guowu Ma Huiying Liu |
| author_facet | Hui Dong Hui Dong Wenyang Zhou Pingping Wang Enjun Zuo Xiaoxia Ying Songling Chai Tao Fei Laidi Jin Chen Chen Guowu Ma Huiying Liu |
| author_sort | Hui Dong |
| collection | DOAJ |
| description | 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. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-14T00:23:13Z |
| publishDate | 2020-03-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-dc4befa58445419ca023379df1e53bd22022-12-22T02:22:53ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-03-01810.3389/fcell.2020.00194532507Comprehensive Analysis of the Genetic and Epigenetic Mechanisms of Osteoporosis and Bone Mineral DensityHui Dong0Hui Dong1Wenyang Zhou2Pingping Wang3Enjun Zuo4Xiaoxia Ying5Songling Chai6Tao Fei7Laidi Jin8Chen Chen9Guowu Ma10Huiying Liu11Department of Oral Prosthodontics, School of Stomatology, Dalian Medical University, Dalian, ChinaDepartment of Stomatology, The First Affiliated Hospital of Dalian Medical University, Dalian, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin, ChinaDepartment of Oral Prosthodontics, School of Stomatology, Dalian Medical University, Dalian, ChinaDepartment of Oral Prosthodontics, School of Stomatology, Dalian Medical University, Dalian, ChinaDepartment of Oral Prosthodontics, School of Stomatology, Dalian Medical University, Dalian, ChinaDepartment of Oral Prosthodontics, School of Stomatology, Dalian Medical University, Dalian, ChinaDepartment of Oral Prosthodontics, School of Stomatology, Dalian Medical University, Dalian, ChinaDepartment of Oral Prosthodontics, School of Stomatology, Dalian Medical University, Dalian, ChinaDepartment of Oral Prosthodontics, School of Stomatology, Dalian Medical University, Dalian, ChinaDepartment of Oral Prosthodontics, School of Stomatology, Dalian Medical University, Dalian, ChinaOsteoporosis 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.https://www.frontiersin.org/article/10.3389/fcell.2020.00194/fullgenome-wide association studyosteoporosisbone mineral densitysummary data-based Mendelian randomizationfunctional element enrichment analysis |
| spellingShingle | Hui Dong Hui Dong Wenyang Zhou Pingping Wang Enjun Zuo Xiaoxia Ying Songling Chai Tao Fei Laidi Jin Chen Chen Guowu Ma Huiying Liu Comprehensive Analysis of the Genetic and Epigenetic Mechanisms of Osteoporosis and Bone Mineral Density Frontiers in Cell and Developmental Biology genome-wide association study osteoporosis bone mineral density summary data-based Mendelian randomization functional element enrichment analysis |
| title | Comprehensive Analysis of the Genetic and Epigenetic Mechanisms of Osteoporosis and Bone Mineral Density |
| title_full | Comprehensive Analysis of the Genetic and Epigenetic Mechanisms of Osteoporosis and Bone Mineral Density |
| title_fullStr | Comprehensive Analysis of the Genetic and Epigenetic Mechanisms of Osteoporosis and Bone Mineral Density |
| title_full_unstemmed | Comprehensive Analysis of the Genetic and Epigenetic Mechanisms of Osteoporosis and Bone Mineral Density |
| title_short | Comprehensive Analysis of the Genetic and Epigenetic Mechanisms of Osteoporosis and Bone Mineral Density |
| title_sort | comprehensive analysis of the genetic and epigenetic mechanisms of osteoporosis and bone mineral density |
| topic | genome-wide association study osteoporosis bone mineral density summary data-based Mendelian randomization functional element enrichment analysis |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00194/full |
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