Integrating genome-wide association study with regulatory SNP annotations identified novel candidate genes for osteoporosis
Aims: Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD. Methods: We conducted an in...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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The British Editorial Society of Bone & Joint Surgery
2023-02-01
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| Series: | Bone & Joint Research |
| Subjects: | |
| Online Access: | https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.122.BJR-2022-0206.R1 |
| _version_ | 1797895398634815488 |
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| author | Yumeng Jia Xin Qi Mei Ma Shiqiang Cheng Bolun Cheng Chujun Liang Xiong Guo Feng Zhang |
| author_facet | Yumeng Jia Xin Qi Mei Ma Shiqiang Cheng Bolun Cheng Chujun Liang Xiong Guo Feng Zhang |
| author_sort | Yumeng Jia |
| collection | DOAJ |
| description | Aims: Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD. Methods: We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects. Results: Through discovery and replication integrative analysis for BMD GWAS and rSNP annotation database, we identified 36 common BMD-associated genes for BMD irrespective of regulatory elements, such as FAM3C (pdiscovery GWAS = 1.21 × 10-25, preplication GWAS = 1.80 × 10-12), CCDC170 (pdiscovery GWAS = 1.23 × 10-11, preplication GWAS = 3.22 × 10-9), and SOX6 (pdiscovery GWAS = 4.41 × 10-15, preplication GWAS = 6.57 × 10-14). Then, for the 36 common target genes, multiple gene ontology (GO) terms were detected for BMD such as positive regulation of cartilage development (p = 9.27 × 10-3) and positive regulation of chondrocyte differentiation (p = 9.27 × 10-3). Conclusion: We explored the potential roles of rSNP in the genetic mechanisms of BMD and identified multiple candidate genes. Our study results support the implication of regulatory genetic variants in the development of OP. Cite this article: Bone Joint Res 2023;12(2):147–154. |
| first_indexed | 2024-04-10T07:24:55Z |
| format | Article |
| id | doaj.art-3c361bb389e849469593c6a35be14f35 |
| institution | Directory Open Access Journal |
| issn | 2046-3758 |
| language | English |
| last_indexed | 2024-04-10T07:24:55Z |
| publishDate | 2023-02-01 |
| publisher | The British Editorial Society of Bone & Joint Surgery |
| record_format | Article |
| series | Bone & Joint Research |
| spelling | doaj.art-3c361bb389e849469593c6a35be14f352023-02-24T07:27:23ZengThe British Editorial Society of Bone & Joint SurgeryBone & Joint Research2046-37582023-02-0112214715410.1302/2046-3758.122.BJR-2022-0206.R1Integrating genome-wide association study with regulatory SNP annotations identified novel candidate genes for osteoporosisYumeng Jia0Xin Qi1Mei Ma2Shiqiang Cheng3Bolun Cheng4Chujun Liang5Xiong Guo6Feng Zhang7School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, ChinaPrecision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, ChinaSchool of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, ChinaSchool of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, ChinaSchool of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, ChinaSchool of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, ChinaSchool of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, ChinaSchool of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, ChinaAims: Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD. Methods: We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects. Results: Through discovery and replication integrative analysis for BMD GWAS and rSNP annotation database, we identified 36 common BMD-associated genes for BMD irrespective of regulatory elements, such as FAM3C (pdiscovery GWAS = 1.21 × 10-25, preplication GWAS = 1.80 × 10-12), CCDC170 (pdiscovery GWAS = 1.23 × 10-11, preplication GWAS = 3.22 × 10-9), and SOX6 (pdiscovery GWAS = 4.41 × 10-15, preplication GWAS = 6.57 × 10-14). Then, for the 36 common target genes, multiple gene ontology (GO) terms were detected for BMD such as positive regulation of cartilage development (p = 9.27 × 10-3) and positive regulation of chondrocyte differentiation (p = 9.27 × 10-3). Conclusion: We explored the potential roles of rSNP in the genetic mechanisms of BMD and identified multiple candidate genes. Our study results support the implication of regulatory genetic variants in the development of OP. Cite this article: Bone Joint Res 2023;12(2):147–154.https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.122.BJR-2022-0206.R1osteoporosisbone mineral densityregulatory single nucleotide polymorphismgenome-wide association studiesbone mineral density (bmd)single nucleotide polymorphismscartilagechondrocytemetabolic bone diseasemesenchymal stem cell (msc)hiposteoblastsrnas |
| spellingShingle | Yumeng Jia Xin Qi Mei Ma Shiqiang Cheng Bolun Cheng Chujun Liang Xiong Guo Feng Zhang Integrating genome-wide association study with regulatory SNP annotations identified novel candidate genes for osteoporosis Bone & Joint Research osteoporosis bone mineral density regulatory single nucleotide polymorphism genome-wide association studies bone mineral density (bmd) single nucleotide polymorphisms cartilage chondrocyte metabolic bone disease mesenchymal stem cell (msc) hip osteoblasts rnas |
| title | Integrating genome-wide association study with regulatory SNP annotations identified novel candidate genes for osteoporosis |
| title_full | Integrating genome-wide association study with regulatory SNP annotations identified novel candidate genes for osteoporosis |
| title_fullStr | Integrating genome-wide association study with regulatory SNP annotations identified novel candidate genes for osteoporosis |
| title_full_unstemmed | Integrating genome-wide association study with regulatory SNP annotations identified novel candidate genes for osteoporosis |
| title_short | Integrating genome-wide association study with regulatory SNP annotations identified novel candidate genes for osteoporosis |
| title_sort | integrating genome wide association study with regulatory snp annotations identified novel candidate genes for osteoporosis |
| topic | osteoporosis bone mineral density regulatory single nucleotide polymorphism genome-wide association studies bone mineral density (bmd) single nucleotide polymorphisms cartilage chondrocyte metabolic bone disease mesenchymal stem cell (msc) hip osteoblasts rnas |
| url | https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.122.BJR-2022-0206.R1 |
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