Assessment of relationships between epigenetic age acceleration and multiple sclerosis: a bidirectional mendelian randomization study
Abstract Background The DNA methylation-based epigenetic clocks are increasingly recognized for their precision in predicting aging and its health implications. Although prior research has identified connections between accelerated epigenetic aging and multiple sclerosis, the chronological and causa...
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BMC
2025-01-01
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| Series: | Epigenetics & Chromatin |
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| Online Access: | https://doi.org/10.1186/s13072-025-00567-9 |
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| author | Hongwei Liu Hanqing Zhang Zhaoxu Yin Miaomiao Hou |
| author_facet | Hongwei Liu Hanqing Zhang Zhaoxu Yin Miaomiao Hou |
| author_sort | Hongwei Liu |
| collection | DOAJ |
| description | Abstract Background The DNA methylation-based epigenetic clocks are increasingly recognized for their precision in predicting aging and its health implications. Although prior research has identified connections between accelerated epigenetic aging and multiple sclerosis, the chronological and causative aspects of these relationships are yet to be elucidated. Our research seeks to clarify these potential causal links through a bidirectional Mendelian randomization study. Methods This analysis employed statistics approaches from genome-wide association studies related to various epigenetic clocks (GrimAge, HannumAge, PhenoAge, and HorvathAge) and multiple sclerosis, utilizing robust instrumental variables from the Edinburgh DataShare (n = 34,710) and the International Multiple Sclerosis Genetics Consortium (including 24,091 controls and 14,498 cases). We applied the inverse-variance weighted approach as our main method for Mendelian randomization, with additional sensitivity analyses to explore underlying heterogeneity and pleiotropy. Results Using summary-based Mendelian randomization, we found that HannumAge was associated with multiple sclerosis (OR = 1.071, 95%CI:1.006–1.140, p = 0.033, by inverse-variance weighted). The results suggest that an increase in epigenetic age acceleration of HannumAge promotes the risk of multiple sclerosis. In reverse Mendelian randomization analysis, no evidence of a clear causal association of multiple sclerosis on epigenetic age acceleration was identified. Conclusions Our Mendelian randomization analysis revealed that epigenetic age acceleration of HannumAge was causally associated with multiple sclerosis, and provided novel insights for further mechanistic and clinical studies of epigenetic age acceleration-mediated multiple sclerosis. |
| format | Article |
| id | doaj-art-8e89d6133e23406cac9fe84ae2e176b6 |
| institution | Kabale University |
| issn | 1756-8935 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj-art-8e89d6133e23406cac9fe84ae2e176b62025-02-02T12:43:05ZengBMCEpigenetics & Chromatin1756-89352025-01-0118111010.1186/s13072-025-00567-9Assessment of relationships between epigenetic age acceleration and multiple sclerosis: a bidirectional mendelian randomization studyHongwei Liu0Hanqing Zhang1Zhaoxu Yin2Miaomiao Hou3Department of Neurology, Taiyuan Central HospitalDepartment of Neurology, The Fourth Affiliated Hospital of Nanjing Medical UniversityDepartment of Neurology, Taiyuan Central HospitalDepartment of Neurology, Tongji Shanxi Hospital, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical UniversityAbstract Background The DNA methylation-based epigenetic clocks are increasingly recognized for their precision in predicting aging and its health implications. Although prior research has identified connections between accelerated epigenetic aging and multiple sclerosis, the chronological and causative aspects of these relationships are yet to be elucidated. Our research seeks to clarify these potential causal links through a bidirectional Mendelian randomization study. Methods This analysis employed statistics approaches from genome-wide association studies related to various epigenetic clocks (GrimAge, HannumAge, PhenoAge, and HorvathAge) and multiple sclerosis, utilizing robust instrumental variables from the Edinburgh DataShare (n = 34,710) and the International Multiple Sclerosis Genetics Consortium (including 24,091 controls and 14,498 cases). We applied the inverse-variance weighted approach as our main method for Mendelian randomization, with additional sensitivity analyses to explore underlying heterogeneity and pleiotropy. Results Using summary-based Mendelian randomization, we found that HannumAge was associated with multiple sclerosis (OR = 1.071, 95%CI:1.006–1.140, p = 0.033, by inverse-variance weighted). The results suggest that an increase in epigenetic age acceleration of HannumAge promotes the risk of multiple sclerosis. In reverse Mendelian randomization analysis, no evidence of a clear causal association of multiple sclerosis on epigenetic age acceleration was identified. Conclusions Our Mendelian randomization analysis revealed that epigenetic age acceleration of HannumAge was causally associated with multiple sclerosis, and provided novel insights for further mechanistic and clinical studies of epigenetic age acceleration-mediated multiple sclerosis.https://doi.org/10.1186/s13072-025-00567-9Multiple sclerosisEpigenetic age accelerationEpigenetic clockMendelian randomizationGenome-wide association studies |
| spellingShingle | Hongwei Liu Hanqing Zhang Zhaoxu Yin Miaomiao Hou Assessment of relationships between epigenetic age acceleration and multiple sclerosis: a bidirectional mendelian randomization study Epigenetics & Chromatin Multiple sclerosis Epigenetic age acceleration Epigenetic clock Mendelian randomization Genome-wide association studies |
| title | Assessment of relationships between epigenetic age acceleration and multiple sclerosis: a bidirectional mendelian randomization study |
| title_full | Assessment of relationships between epigenetic age acceleration and multiple sclerosis: a bidirectional mendelian randomization study |
| title_fullStr | Assessment of relationships between epigenetic age acceleration and multiple sclerosis: a bidirectional mendelian randomization study |
| title_full_unstemmed | Assessment of relationships between epigenetic age acceleration and multiple sclerosis: a bidirectional mendelian randomization study |
| title_short | Assessment of relationships between epigenetic age acceleration and multiple sclerosis: a bidirectional mendelian randomization study |
| title_sort | assessment of relationships between epigenetic age acceleration and multiple sclerosis a bidirectional mendelian randomization study |
| topic | Multiple sclerosis Epigenetic age acceleration Epigenetic clock Mendelian randomization Genome-wide association studies |
| url | https://doi.org/10.1186/s13072-025-00567-9 |
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