ArticleBrain and behavior2025
Causal Associations of Epigenetic Age Acceleration With Stroke and Its Functional Outcome: A Two-Sample, Two-Step Mendelian Randomization Study.
Article in Brain and behavior, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEmerging 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.
methodsWe 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).
resultsTwo-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
conclusionsOur 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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