Causal Associations of Epigenetic Age Acceleration With Stroke and Its Functional Outcome: A Two-Sample, Two-Step Mendelian Randomization Study

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES Brain and Behavior Pub Date : 2025-03-18 DOI:10.1002/brb3.70412

Baizhi Qiu, Shuyang Wen, Zifan Li, Yuxin Cai, Qi Zhang, Yuting Zeng, Shuqi Zheng, Zhishan Lin, Yupeng Xiao, Jihua Zou, Guozhi Huang, Qing Zeng

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Abstract

Background

Emerging evidence from observational studies suggested that epigenetic age acceleration may result in an increased incidence of stroke and poorer functional outcomes after a stroke. However, the causality of these associations remains controversial and may be confounded by bias. We aimed to investigate the causal effects of epigenetic age on stroke and its functional outcomes.

Methods

We conducted a two-sample Mendelian randomization (MR) analysis to explore the causal relationships between epigenetic age and stroke and its outcomes. Additionally, a two-step MR analysis was performed to investigate whether lifestyle factors affect stroke via epigenetic age. Datasets of epigenetic age were obtained from a recent meta-analysis (n = 34,710), while those of stroke and its outcomes were sourced from the MEGASTROKE (n = 520,000) consortium and Genetics of Ischaemic Stroke Functional Outcome (GISCOME) network (n = 6165).

Results

Two-sample MR analysis revealed a causal relationship between PhenoAge and small vessel stroke (SVS) (OR = 1.07; 95% CI, 1.03–1.12; p = 2.01 × 10⁻³). Mediation analysis through two-step MR indicated that the increased risk of SVS due to smoking initiation was partially mediated by PhenoAge, with a mediation proportion of 9.5% (95% CI, 1.6%–20.6%). No causal relationships were identified between epigenetic age and stroke outcomes.

Conclusions

Our study supports using epigenetic age as a biomarker to predict stroke occurrence. Interventions specifically aimed at decelerating epigenetic aging, such as specific lifestyle changes, offer effective strategies for reducing stroke risk.

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来源期刊

Brain and Behavior BEHAVIORAL SCIENCES-NEUROSCIENCES

CiteScore

5.30

自引率

0.00%

发文量

352

审稿时长

14 weeks

期刊介绍： Brain and Behavior is supported by other journals published by Wiley, including a number of society-owned journals. The journals listed below support Brain and Behavior and participate in the Manuscript Transfer Program by referring articles of suitable quality and offering authors the option to have their paper, with any peer review reports, automatically transferred to Brain and Behavior. * [Acta Psychiatrica Scandinavica](https://publons.com/journal/1366/acta-psychiatrica-scandinavica) * [Addiction Biology](https://publons.com/journal/1523/addiction-biology) * [Aggressive Behavior](https://publons.com/journal/3611/aggressive-behavior) * [Brain Pathology](https://publons.com/journal/1787/brain-pathology) * [Child: Care, Health and Development](https://publons.com/journal/6111/child-care-health-and-development) * [Criminal Behaviour and Mental Health](https://publons.com/journal/3839/criminal-behaviour-and-mental-health) * [Depression and Anxiety](https://publons.com/journal/1528/depression-and-anxiety) * Developmental Neurobiology * [Developmental Science](https://publons.com/journal/1069/developmental-science) * [European Journal of Neuroscience](https://publons.com/journal/1441/european-journal-of-neuroscience) * [Genes, Brain and Behavior](https://publons.com/journal/1635/genes-brain-and-behavior) * [GLIA](https://publons.com/journal/1287/glia) * [Hippocampus](https://publons.com/journal/1056/hippocampus) * [Human Brain Mapping](https://publons.com/journal/500/human-brain-mapping) * [Journal for the Theory of Social Behaviour](https://publons.com/journal/7330/journal-for-the-theory-of-social-behaviour) * [Journal of Comparative Neurology](https://publons.com/journal/1306/journal-of-comparative-neurology) * [Journal of Neuroimaging](https://publons.com/journal/6379/journal-of-neuroimaging) * [Journal of Neuroscience Research](https://publons.com/journal/2778/journal-of-neuroscience-research) * [Journal of Organizational Behavior](https://publons.com/journal/1123/journal-of-organizational-behavior) * [Journal of the Peripheral Nervous System](https://publons.com/journal/3929/journal-of-the-peripheral-nervous-system) * [Muscle & Nerve](https://publons.com/journal/4448/muscle-and-nerve) * [Neural Pathology and Applied Neurobiology](https://publons.com/journal/2401/neuropathology-and-applied-neurobiology)