Abstract
Background
Clinical studies suggest a strong link between extensive perivascular space (EPVS) and ischemic stroke (IS), including its subtypes, and transient ischemic attack (TIA), but it's uncertain if the relationship is genetically causal.
Methods
We utilize summary 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 relationship between EPVS and IS, its subtypes, and TIA. We apply multivariable MR to mitigate potential confounding factors and conduct sensitivity analyses to enhance result robustness. Subsequently, meta-analysis is utilized to integrate causal relationships between EPVS in different locations 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 exposures 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 = 5.95E-07). Additionally, there appears to be a potential increase in extensive basal ganglia perivascular space burden following IS and TIA.
Conclusion
Extensive white matter perivascular space burden and extensive basal ganglia perivascular space burden may serve as important indicators for predicting IS.