Genetically Predicted Smoking and Alcohol Consumption and Functional Outcome After Ischemic Stroke

Smoking and alcohol consumption have been adversely associated with poststroke outcome in traditional epidemiologic studies. The present study explored the association of genetically predicted smoking and alcohol consumption on poststroke outcomes using the mendelian randomization (MR) framework.Instrumental variables for smoking initiation and alcohol consumption were selected from a genome-wide association study data of European ancestry individuals. Summary-level data for functional outcome after ischemic stroke were obtained from the Genetics of Ischemic Stroke Functional Outcome network study of European ancestry patients. The univariable and multivariable inverse-variance weighted MR methods were performed to obtain the causal estimates. The weighted median, MR-robust adjusted profile score, and MR-Egger regression approaches were adopted as sensitivity analyses. Q and I2 statistics were used to evaluate heterogeneity in MR estimates across variants.Genetic predisposition to smoking initiation was associated with worse functional outcome after ischemic stroke in univariable inverse-variance weighted MR analysis (odds ratio [OR] 1.48; 95% CI 1.08-2.01, p = 0.013). This association remained significant when adjusting for genetically predicted alcohol consumption in multivariable MR analyses (OR 1.56; 95% CI 1.05-2.32, p = 0.027). Genetically predicted alcohol consumption was not associated with functional outcome after ischemic stroke (p > 0.05). Sensitivity analyses with other approaches and in analyses restricted to models without adjustment for baseline stroke severity produced similar results, and no evidence of heterogeneity in MR estimates between variants was detected (p > 0.05).Our results provide genetic support for a causal association of smoking with worse functional outcome after ischemic stroke and have important implications for poststroke recovery. Smoking cessation and avoidance should be promoted in patients with ischemic stroke.