Assessing the Causal Association between Biological Aging Biomarkers and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization Study
Biological aging biomarkers, such as leukocyte telomere length (LTL) and epigenetic clocks, have been associated with the risk of cerebral small vessel disease (CSVD) in several observational studies. However, it is unclear whether LTL or epigenetic clocks play causal roles as prognostic biomarkers...
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MDPI AG
2023-04-01
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| Online Access: | https://www.mdpi.com/2079-7737/12/5/660 |
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| author | Biying Lin Yuzhu Mu Zhongxiang Ding |
| author_facet | Biying Lin Yuzhu Mu Zhongxiang Ding |
| author_sort | Biying Lin |
| collection | DOAJ |
| description | Biological aging biomarkers, such as leukocyte telomere length (LTL) and epigenetic clocks, have been associated with the risk of cerebral small vessel disease (CSVD) in several observational studies. However, it is unclear whether LTL or epigenetic clocks play causal roles as prognostic biomarkers in the development of CSVD. We performed a Mendelian randomization (MR) study of LTL and four epigenetic clocks on ten subclinical and clinical CSVD measures. We obtained genome-wide association (GWAS) data for LTL from the UK Biobank (N = 472,174). Data on epigenetic clocks were derived from a meta-analysis (N = 34,710), and CSVD data (N cases =1293–18,381; N controls = 25,806–105,974) were extracted from the Cerebrovascular Disease Knowledge Portal. We found that genetically determined LTL and epigenetic clocks were not individually associated with ten measures of CSVD (IVW <i>p</i> > 0.05), and this result was consistent across sensitivity analyses. Our findings imply that LTL and epigenetic clocks may not help in predicting CSVD development as causal prognostic biomarkers. Further studies are needed to illustrate the potential of reverse biological aging in serving as an effective form of preventive therapy for CSVD. |
| first_indexed | 2024-03-11T03:55:57Z |
| format | Article |
| id | doaj.art-a4c4c54fa6c94e218ec55a13b592bc4f |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-11T03:55:57Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-a4c4c54fa6c94e218ec55a13b592bc4f2023-11-18T00:32:36ZengMDPI AGBiology2079-77372023-04-0112566010.3390/biology12050660Assessing the Causal Association between Biological Aging Biomarkers and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization StudyBiying Lin0Yuzhu Mu1Zhongxiang Ding2Department of Radiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, 261 Huansha Rd., Hangzhou 310006, ChinaDepartment of Radiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, 261 Huansha Rd., Hangzhou 310006, ChinaDepartment of Radiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, 261 Huansha Rd., Hangzhou 310006, ChinaBiological aging biomarkers, such as leukocyte telomere length (LTL) and epigenetic clocks, have been associated with the risk of cerebral small vessel disease (CSVD) in several observational studies. However, it is unclear whether LTL or epigenetic clocks play causal roles as prognostic biomarkers in the development of CSVD. We performed a Mendelian randomization (MR) study of LTL and four epigenetic clocks on ten subclinical and clinical CSVD measures. We obtained genome-wide association (GWAS) data for LTL from the UK Biobank (N = 472,174). Data on epigenetic clocks were derived from a meta-analysis (N = 34,710), and CSVD data (N cases =1293–18,381; N controls = 25,806–105,974) were extracted from the Cerebrovascular Disease Knowledge Portal. We found that genetically determined LTL and epigenetic clocks were not individually associated with ten measures of CSVD (IVW <i>p</i> > 0.05), and this result was consistent across sensitivity analyses. Our findings imply that LTL and epigenetic clocks may not help in predicting CSVD development as causal prognostic biomarkers. Further studies are needed to illustrate the potential of reverse biological aging in serving as an effective form of preventive therapy for CSVD.https://www.mdpi.com/2079-7737/12/5/660cerebral small vessel diseasebiological agingleukocyte telomere lengthepigenetic clockMendelian randomization |
| spellingShingle | Biying Lin Yuzhu Mu Zhongxiang Ding Assessing the Causal Association between Biological Aging Biomarkers and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization Study Biology cerebral small vessel disease biological aging leukocyte telomere length epigenetic clock Mendelian randomization |
| title | Assessing the Causal Association between Biological Aging Biomarkers and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization Study |
| title_full | Assessing the Causal Association between Biological Aging Biomarkers and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization Study |
| title_fullStr | Assessing the Causal Association between Biological Aging Biomarkers and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization Study |
| title_full_unstemmed | Assessing the Causal Association between Biological Aging Biomarkers and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization Study |
| title_short | Assessing the Causal Association between Biological Aging Biomarkers and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization Study |
| title_sort | assessing the causal association between biological aging biomarkers and the development of cerebral small vessel disease a mendelian randomization study |
| topic | cerebral small vessel disease biological aging leukocyte telomere length epigenetic clock Mendelian randomization |
| url | https://www.mdpi.com/2079-7737/12/5/660 |
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