Causal associations between epigenetic age and thromboembolism: a bi-directional two-sample Mendelian randomization study
Abstract Background Thromboembolism is one of the most prevalent cardiovascular conditions affecting the elder population. The associations between epigenetic aging and thromboembolism risks remain incompletely elucidated. Through Mendelian randomization (MR), this research seeks to assess the causa...
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BMC
2025-05-01
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| Series: | Clinical Epigenetics |
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| Online Access: | https://doi.org/10.1186/s13148-025-01875-3 |
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| author | Bowen Jin Yunyan Li Dingyang Li Chi Jing Qunshan Sheng |
| author_facet | Bowen Jin Yunyan Li Dingyang Li Chi Jing Qunshan Sheng |
| author_sort | Bowen Jin |
| collection | DOAJ |
| description | Abstract Background Thromboembolism is one of the most prevalent cardiovascular conditions affecting the elder population. The associations between epigenetic aging and thromboembolism risks remain incompletely elucidated. Through Mendelian randomization (MR), this research seeks to assess the causal links between genetically determined epigenetic aging factors and thromboembolism. Results Genetic variants were extracted from genome-wide association studies (GWAS) under stringent threshold as instrumental variables (IVs). Bi-directional two-sample MR analyses were conducted to determine the direction of causal associations. We employed the inverse variance weighted (IVW), weighted median, weighted mode and MR Egger to estimate the causal effect, with sensitivity analyses such as Cochran’s Q tests, MR-PRESSO and leave-one-out performed to avoid potential heterogeneity and pleiotropy. Our MR analysis revealed a causal association between intrinsic epigenetic age acceleration and deep vein thrombosis of lower extremities (IVW: OR 0.963, 95% CI 0.934–0.992, P = 0.014), and between the genetically determined levels of plasminogen activator inhibitor-1 and other arterial embolism and thrombosis (IVW: OR 1.000, 95% CI 1.000–1.0005, P = 0.029). Causality was also identified between the genetically predicted levels of FGF23 and other arterial embolism and thrombosis (IVW: OR: 1.661, 95% CI 1.051–2.624, P = 0.029) and arterial embolism and thrombosis of lower extremity artery (IVW: OR 1.68, 95% CI 1.031–2.725, P = 0.037). Moreover, bi-directional MR showed reverse effects between portal vein thrombosis and PhenoAge (IVW: OR 0.871, 95% CI 0.765–0.992, P = 0.037) and between venous thromboembolism and GrimAge (IVW: OR 1.186, 95% CI 1.048–1.341, P = 0.007). Sensitivity analysis using Cochran’s Q tests, MR-PRESSO and leave-one-out excluded the influence of heterogeneity, horizontal pleiotropy, and outliers. Conclusion Our results identified a causal association between genetically predicted epigenetic aging factors and thromboembolism. The findings highlight the necessity for further exploration into the underlying etiology of thromboembolism. |
| format | Article |
| id | doaj-art-7d1cb38382564cd8a210ca079ba91ce6 |
| institution | DOAJ |
| issn | 1868-7083 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | Clinical Epigenetics |
| spelling | doaj-art-7d1cb38382564cd8a210ca079ba91ce62025-08-20T03:09:19ZengBMCClinical Epigenetics1868-70832025-05-0117113010.1186/s13148-025-01875-3Causal associations between epigenetic age and thromboembolism: a bi-directional two-sample Mendelian randomization studyBowen Jin0Yunyan Li1Dingyang Li2Chi Jing3Qunshan Sheng4Department of Cardiovascular Surgery, Wuhan Asia Heart HospitalDepartment of Cardiovascular Surgery, Wuhan Asia Heart HospitalDepartment of Cardiovascular Surgery, Wuhan Asia Heart HospitalDepartment of Cardiovascular Surgery, Wuhan Asia Heart HospitalDepartment of Cardiovascular Surgery, Wuhan Asia Heart HospitalAbstract Background Thromboembolism is one of the most prevalent cardiovascular conditions affecting the elder population. The associations between epigenetic aging and thromboembolism risks remain incompletely elucidated. Through Mendelian randomization (MR), this research seeks to assess the causal links between genetically determined epigenetic aging factors and thromboembolism. Results Genetic variants were extracted from genome-wide association studies (GWAS) under stringent threshold as instrumental variables (IVs). Bi-directional two-sample MR analyses were conducted to determine the direction of causal associations. We employed the inverse variance weighted (IVW), weighted median, weighted mode and MR Egger to estimate the causal effect, with sensitivity analyses such as Cochran’s Q tests, MR-PRESSO and leave-one-out performed to avoid potential heterogeneity and pleiotropy. Our MR analysis revealed a causal association between intrinsic epigenetic age acceleration and deep vein thrombosis of lower extremities (IVW: OR 0.963, 95% CI 0.934–0.992, P = 0.014), and between the genetically determined levels of plasminogen activator inhibitor-1 and other arterial embolism and thrombosis (IVW: OR 1.000, 95% CI 1.000–1.0005, P = 0.029). Causality was also identified between the genetically predicted levels of FGF23 and other arterial embolism and thrombosis (IVW: OR: 1.661, 95% CI 1.051–2.624, P = 0.029) and arterial embolism and thrombosis of lower extremity artery (IVW: OR 1.68, 95% CI 1.031–2.725, P = 0.037). Moreover, bi-directional MR showed reverse effects between portal vein thrombosis and PhenoAge (IVW: OR 0.871, 95% CI 0.765–0.992, P = 0.037) and between venous thromboembolism and GrimAge (IVW: OR 1.186, 95% CI 1.048–1.341, P = 0.007). Sensitivity analysis using Cochran’s Q tests, MR-PRESSO and leave-one-out excluded the influence of heterogeneity, horizontal pleiotropy, and outliers. Conclusion Our results identified a causal association between genetically predicted epigenetic aging factors and thromboembolism. The findings highlight the necessity for further exploration into the underlying etiology of thromboembolism.https://doi.org/10.1186/s13148-025-01875-3ThromboembolismEpigenetic aging clocksCausal inferenceMendelian randomization |
| spellingShingle | Bowen Jin Yunyan Li Dingyang Li Chi Jing Qunshan Sheng Causal associations between epigenetic age and thromboembolism: a bi-directional two-sample Mendelian randomization study Clinical Epigenetics Thromboembolism Epigenetic aging clocks Causal inference Mendelian randomization |
| title | Causal associations between epigenetic age and thromboembolism: a bi-directional two-sample Mendelian randomization study |
| title_full | Causal associations between epigenetic age and thromboembolism: a bi-directional two-sample Mendelian randomization study |
| title_fullStr | Causal associations between epigenetic age and thromboembolism: a bi-directional two-sample Mendelian randomization study |
| title_full_unstemmed | Causal associations between epigenetic age and thromboembolism: a bi-directional two-sample Mendelian randomization study |
| title_short | Causal associations between epigenetic age and thromboembolism: a bi-directional two-sample Mendelian randomization study |
| title_sort | causal associations between epigenetic age and thromboembolism a bi directional two sample mendelian randomization study |
| topic | Thromboembolism Epigenetic aging clocks Causal inference Mendelian randomization |
| url | https://doi.org/10.1186/s13148-025-01875-3 |
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