Causal association between air pollution and functional outcome after ischemic stroke: Evidence from 2-sample MR study

Observational studies have shown that air pollution may affect functional outcome following ischemic stroke. Our study aimed to explore the relationship between genetically predicted specific air pollutants and poststroke functional outcomes using the Mendelian randomization (MR) methodology. The instrumental variables for air pollution (nitrogen oxide [NO _x ], nitrogen dioxide [NO ₂ ], PM _2.5 , PM _2.5-10 , and PM ₁₀ ) were derived from whole-genome association study data of individuals of European descent. Summary data for functional outcomes after ischemic stroke were sourced from the Ischemic Stroke Genetics Functional Outcome Network. Primary analysis employed the “IVW” method for 2-sample MR. In sensitivity analysis, Cochran Q test, inverse variance-weighted (IVW) method, and MR-Egger method were used for heterogeneity assessment. In the horizontal pleiotropy analysis, we utilized the MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) test. Finally, the robustness of the results is ensured. Gene prediction suggested no association between several air pollutants and functional outcome after ischemic stroke (PM _2.5 [odds ratio (OR) 0.87; 95% confidence interval (CI) 0.26–2.95; P  = .825], NO _x [OR, 0.77; 95% CI: 0.27–2.21; P  = .629], NO ₂ [OR 1.73; 95% CI: 0.61–4.90; P  = .304], PM _2.5-10 [OR 2.48; 95% CI: 0.28–22.12; P  = .416], and PM ₁₀ [OR 2.54; 95% CI: 0.41–15.87; P  = .319]). The supplementary MR methods confirmed similar results. Further analysis, not adjusted for stroke severity, supports these findings. Air pollutants (NO _x , NO ₂ , PM _2.5 , PM _2.5-10 and PM ₁₀ ) may not have an impact on functional outcome after ischemic stroke.