Unraveling the causal impact of smoking and its DNA methylation signatures on cardiovascular disease: Mendelian randomization and colocalization analysis
Abstract Background To explore the mechanisms linking smoking to cardiovascular diseases (CVDs) from an epigenetic perspective. Methods Mendelian Randomization (MR) analysis was performed to assess the causal effects of smoking behavior and DNA methylation levels at smoking-related CpG sites on nine...
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BMC
2025-01-01
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| Series: | Clinical Epigenetics |
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| Online Access: | https://doi.org/10.1186/s13148-024-01808-6 |
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| author | Si Cao Youjie Zeng Ke Pang Minghua Chen Ren Guo Nayiyuan Wu Chao Fang Huiyin Deng Xiaoyi Zhang Xiaohui Xie Wen Ouyang Heng Yang |
| author_facet | Si Cao Youjie Zeng Ke Pang Minghua Chen Ren Guo Nayiyuan Wu Chao Fang Huiyin Deng Xiaoyi Zhang Xiaohui Xie Wen Ouyang Heng Yang |
| author_sort | Si Cao |
| collection | DOAJ |
| description | Abstract Background To explore the mechanisms linking smoking to cardiovascular diseases (CVDs) from an epigenetic perspective. Methods Mendelian Randomization (MR) analysis was performed to assess the causal effects of smoking behavior and DNA methylation levels at smoking-related CpG sites on nine CVDs, including aortic aneurysm, atrial fibrillation, coronary atherosclerosis, coronary heart disease, heart failure, intracerebral hemorrhage, ischemic stroke, myocardial infarction, subarachnoid hemorrhage. Colocalization analysis was used to further identify key smoking-related CpG sites from the MR causal estimates. Reactome enrichment analysis was used to elucidate the potential mechanisms. Results MR analysis indicates that smoking behaviors are significantly associated with an increased risk of nine CVDs (OR > 1, P < 0.05). Through MR and colocalization analysis, five key smoking-related CpG sites were ultimately determined. DNA methylation alteration at cg25313468 (located in the TSS1500 region of REST) is simultaneously associated with the risk of atrial fibrillation, coronary atherosclerosis, coronary heart disease, and myocardial infarction. Additionally, cg21647257 (located in the TSS200 region of CLIP3) is associated with the risk of atrial fibrillation; cg06197751 (located in SGEF gene body) and cg07520810 (located in ARID5B gene body) are associated with the risk of coronary atherosclerosis; cg16822035 (located in MCF2L gene body) is associated with the risk of myocardial infarction. Enrichment analysis suggests that phosphatase and tensin homologue (PTEN) may be involved in the downstream mechanisms of cg25313468 (REST). Conclusion This study uncovers the relationship between smoking, DNA methylation, and CVDs, providing new insights into the pathogenic effect of smoking on CVDs from an epigenetic perspective. |
| format | Article |
| id | doaj-art-ec51dcf65d0c41be8fe8111097a39b6d |
| institution | Kabale University |
| issn | 1868-7083 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj-art-ec51dcf65d0c41be8fe8111097a39b6d2025-01-05T12:33:58ZengBMCClinical Epigenetics1868-70832025-01-0117111310.1186/s13148-024-01808-6Unraveling the causal impact of smoking and its DNA methylation signatures on cardiovascular disease: Mendelian randomization and colocalization analysisSi Cao0Youjie Zeng1Ke Pang2Minghua Chen3Ren Guo4Nayiyuan Wu5Chao Fang6Huiyin Deng7Xiaoyi Zhang8Xiaohui Xie9Wen Ouyang10Heng Yang11Department of Anesthesiology, Third Xiangya Hospital, Central South UniversityDepartment of Anesthesiology, Third Xiangya Hospital, Central South UniversityDepartment of Anesthesiology, Third Xiangya Hospital, Central South UniversityDepartment of Anesthesiology, Third Xiangya Hospital, Central South UniversityDepartment of Pharmacy, Third Xiangya Hospital, Central South UniversityThe Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer HospitalThe Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer HospitalDepartment of Anesthesiology, Third Xiangya Hospital, Central South UniversityDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of MedicineDepartment of Medicine, Baylor College of MedicineDepartment of Anesthesiology, Third Xiangya Hospital, Central South UniversityDepartment of Neurology, Third Xiangya Hospital, Central South UniversityAbstract Background To explore the mechanisms linking smoking to cardiovascular diseases (CVDs) from an epigenetic perspective. Methods Mendelian Randomization (MR) analysis was performed to assess the causal effects of smoking behavior and DNA methylation levels at smoking-related CpG sites on nine CVDs, including aortic aneurysm, atrial fibrillation, coronary atherosclerosis, coronary heart disease, heart failure, intracerebral hemorrhage, ischemic stroke, myocardial infarction, subarachnoid hemorrhage. Colocalization analysis was used to further identify key smoking-related CpG sites from the MR causal estimates. Reactome enrichment analysis was used to elucidate the potential mechanisms. Results MR analysis indicates that smoking behaviors are significantly associated with an increased risk of nine CVDs (OR > 1, P < 0.05). Through MR and colocalization analysis, five key smoking-related CpG sites were ultimately determined. DNA methylation alteration at cg25313468 (located in the TSS1500 region of REST) is simultaneously associated with the risk of atrial fibrillation, coronary atherosclerosis, coronary heart disease, and myocardial infarction. Additionally, cg21647257 (located in the TSS200 region of CLIP3) is associated with the risk of atrial fibrillation; cg06197751 (located in SGEF gene body) and cg07520810 (located in ARID5B gene body) are associated with the risk of coronary atherosclerosis; cg16822035 (located in MCF2L gene body) is associated with the risk of myocardial infarction. Enrichment analysis suggests that phosphatase and tensin homologue (PTEN) may be involved in the downstream mechanisms of cg25313468 (REST). Conclusion This study uncovers the relationship between smoking, DNA methylation, and CVDs, providing new insights into the pathogenic effect of smoking on CVDs from an epigenetic perspective.https://doi.org/10.1186/s13148-024-01808-6Mendelian randomizationCigarette smokingDNA methylationCardiovascular diseasesCausal inferenceRisk factors |
| spellingShingle | Si Cao Youjie Zeng Ke Pang Minghua Chen Ren Guo Nayiyuan Wu Chao Fang Huiyin Deng Xiaoyi Zhang Xiaohui Xie Wen Ouyang Heng Yang Unraveling the causal impact of smoking and its DNA methylation signatures on cardiovascular disease: Mendelian randomization and colocalization analysis Clinical Epigenetics Mendelian randomization Cigarette smoking DNA methylation Cardiovascular diseases Causal inference Risk factors |
| title | Unraveling the causal impact of smoking and its DNA methylation signatures on cardiovascular disease: Mendelian randomization and colocalization analysis |
| title_full | Unraveling the causal impact of smoking and its DNA methylation signatures on cardiovascular disease: Mendelian randomization and colocalization analysis |
| title_fullStr | Unraveling the causal impact of smoking and its DNA methylation signatures on cardiovascular disease: Mendelian randomization and colocalization analysis |
| title_full_unstemmed | Unraveling the causal impact of smoking and its DNA methylation signatures on cardiovascular disease: Mendelian randomization and colocalization analysis |
| title_short | Unraveling the causal impact of smoking and its DNA methylation signatures on cardiovascular disease: Mendelian randomization and colocalization analysis |
| title_sort | unraveling the causal impact of smoking and its dna methylation signatures on cardiovascular disease mendelian randomization and colocalization analysis |
| topic | Mendelian randomization Cigarette smoking DNA methylation Cardiovascular diseases Causal inference Risk factors |
| url | https://doi.org/10.1186/s13148-024-01808-6 |
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