Causal association between epigenetic age acceleration and two pulmonary vascular diseases: pulmonary arterial hypertension and pulmonary embolism—a bidirectional Mendelian study
Abstract Background Pulmonary arterial hypertension (PAH) is a relatively rare but severe disease with a poor prognosis. Pulmonary embolism (PE) is a serious condition that can cause sudden death. Epigenetic age acceleration (EAA) is a robust indicator derived from the DNA methylation-based epigenet...
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2024-11-01
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author | Jun Tong Chuanxue Wan An Wang Mengqi Chen Binqian Ruan Jieyan Shen |
author_facet | Jun Tong Chuanxue Wan An Wang Mengqi Chen Binqian Ruan Jieyan Shen |
author_sort | Jun Tong |
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description | Abstract Background Pulmonary arterial hypertension (PAH) is a relatively rare but severe disease with a poor prognosis. Pulmonary embolism (PE) is a serious condition that can cause sudden death. Epigenetic age acceleration (EAA) is a robust indicator derived from the DNA methylation-based epigenetic clock, which can predict the extent of aging. It has been proved that the epigenetic clock and EAA are associated with many cardiovascular diseases, while their associations with PAH and PE remain inconclusive. Our study aims to investigate the associations among these factors. Method By harnessing summary-level data from large-scale genome-wide association studies (GWAS), we designed a two-sample bidirectional Mendelian randomization (MR) analysis to assess the causal associations between measures of three epigenetic clocks, including GrimAge acceleration (n = 34,467), Hannum Age acceleration (n = 34,449) and PhenoAge acceleration (n = 34,463) and PAH (including 125 cases and 162,837 controls), as well as PE (including 3940 cases and 480,658 controls). The inverse variance-weighted (IVW) method was used as the primary method for MR analysis. Other methods, such as MR egger and weighted mode, served as complements to the IVW approach, were also applied in the analyses. Then, the MR pleiotropy test and MR-PRESSO test, which are effective tools for quality control of MR analysis, were subsequently used to ensure the accuracy of the study. Results The forward MR analysis indicated that all three epigenetic clocks had no significant effects on PAH or PE. The reverse analysis indicated that the onset and progression of PAH and PE had insignificant effects on three epigenetic clocks. The results of the quality control assessment confirmed that our findings were reliable. Conclusion Our two-sample bidirectional MR analysis suggested that there is no significant association between epigenetic clocks and these two pulmonary vascular diseases. |
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spelling | doaj-art-9c1d1c6dc7094cfd87af84b66a399c282024-12-01T12:31:51ZengBMCClinical Epigenetics1868-70832024-11-011611910.1186/s13148-024-01778-9Causal association between epigenetic age acceleration and two pulmonary vascular diseases: pulmonary arterial hypertension and pulmonary embolism—a bidirectional Mendelian studyJun Tong0Chuanxue Wan1An Wang2Mengqi Chen3Binqian Ruan4Jieyan Shen5Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Background Pulmonary arterial hypertension (PAH) is a relatively rare but severe disease with a poor prognosis. Pulmonary embolism (PE) is a serious condition that can cause sudden death. Epigenetic age acceleration (EAA) is a robust indicator derived from the DNA methylation-based epigenetic clock, which can predict the extent of aging. It has been proved that the epigenetic clock and EAA are associated with many cardiovascular diseases, while their associations with PAH and PE remain inconclusive. Our study aims to investigate the associations among these factors. Method By harnessing summary-level data from large-scale genome-wide association studies (GWAS), we designed a two-sample bidirectional Mendelian randomization (MR) analysis to assess the causal associations between measures of three epigenetic clocks, including GrimAge acceleration (n = 34,467), Hannum Age acceleration (n = 34,449) and PhenoAge acceleration (n = 34,463) and PAH (including 125 cases and 162,837 controls), as well as PE (including 3940 cases and 480,658 controls). The inverse variance-weighted (IVW) method was used as the primary method for MR analysis. Other methods, such as MR egger and weighted mode, served as complements to the IVW approach, were also applied in the analyses. Then, the MR pleiotropy test and MR-PRESSO test, which are effective tools for quality control of MR analysis, were subsequently used to ensure the accuracy of the study. Results The forward MR analysis indicated that all three epigenetic clocks had no significant effects on PAH or PE. The reverse analysis indicated that the onset and progression of PAH and PE had insignificant effects on three epigenetic clocks. The results of the quality control assessment confirmed that our findings were reliable. Conclusion Our two-sample bidirectional MR analysis suggested that there is no significant association between epigenetic clocks and these two pulmonary vascular diseases.https://doi.org/10.1186/s13148-024-01778-9Pulmonary hypertensionPulmonary embolismEpigenetic age accelerationEpigenetic clockMendelian randomization |
spellingShingle | Jun Tong Chuanxue Wan An Wang Mengqi Chen Binqian Ruan Jieyan Shen Causal association between epigenetic age acceleration and two pulmonary vascular diseases: pulmonary arterial hypertension and pulmonary embolism—a bidirectional Mendelian study Clinical Epigenetics Pulmonary hypertension Pulmonary embolism Epigenetic age acceleration Epigenetic clock Mendelian randomization |
title | Causal association between epigenetic age acceleration and two pulmonary vascular diseases: pulmonary arterial hypertension and pulmonary embolism—a bidirectional Mendelian study |
title_full | Causal association between epigenetic age acceleration and two pulmonary vascular diseases: pulmonary arterial hypertension and pulmonary embolism—a bidirectional Mendelian study |
title_fullStr | Causal association between epigenetic age acceleration and two pulmonary vascular diseases: pulmonary arterial hypertension and pulmonary embolism—a bidirectional Mendelian study |
title_full_unstemmed | Causal association between epigenetic age acceleration and two pulmonary vascular diseases: pulmonary arterial hypertension and pulmonary embolism—a bidirectional Mendelian study |
title_short | Causal association between epigenetic age acceleration and two pulmonary vascular diseases: pulmonary arterial hypertension and pulmonary embolism—a bidirectional Mendelian study |
title_sort | causal association between epigenetic age acceleration and two pulmonary vascular diseases pulmonary arterial hypertension and pulmonary embolism a bidirectional mendelian study |
topic | Pulmonary hypertension Pulmonary embolism Epigenetic age acceleration Epigenetic clock Mendelian randomization |
url | https://doi.org/10.1186/s13148-024-01778-9 |
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