摘要Objectives:Clinical studies suggest a strong link between extensive perivascular space(EPVS)and ischemic stroke(IS),including its subtypes,and tran-sient ischemic attack(TIA),but it's uncertain if the rela-tionship is genetically causal.Methods:We utilize sum-mary data from large-scale Genome-wide Association Studies(GWAS)to investigate the association between EPVS in different locations and IS,its subtypes,and TIA through Mendelian randomization(MR)analysis.Various MR methods are employed to assess the causal relation-ship between EPVS and IS,its subtypes,and TIA.We ap-ply multivariable MR to mitigate potential confounding factors and conduct sensitivity analyses to enhance result robustness.Subsequently,meta-analysis is utilized to in-tegrate causal relationships between EPVS in different lo-cations and IS from various sources.Additionally,reverse MR is employed to observe the impact of various IS types on EPVS.Finally,linkage disequilibrium score regression is conducted to assess genetic correlations between expo-sures and outcomes.Results:EPVS burden in both the white matter(OR=1.12;95%CI:1.01-1.25;P=0.04)and the basal ganglia(OR=1.57;95%CI:1.30-1.89;P<0.01)are significant risk factors for IS.EPVS burden in the basal ganglia is also a risk for IS(small-vessel)(OR=4.56;95%CI:2.57-8.27;P=5.95×107).Additionally,there appears to be a potential increase in extensive basal ganglia perivascular space burden following IS and TIA.Conclusions:Extensive white matter perivascular space burden and extensive basal ganglia perivascular space burden may serve as important indicators for predicting IS.