Genetically Predicted Sleep Traits and Functional Outcome After Ischemic Stroke: A Mendelian Randomization Study

Sleep traits can have implications for ischemic stroke recovery in observational studies. The purpose of our present study was to explore the relationship between genetically predicted sleep traits and post-stroke functional outcomes with Mendelian randomization (MR) method.Instrumental variables for insomnia and sleep duration were adopted from genome-wide association studies data of European ancestry individuals. Summary data for functional outcome after ischemic stroke was retrieved from the Genetics of Ischemic Stroke Functional Outcome network. Inverse-variance weighted approach was adopted as the main analyses. Alternative MR approaches were used in sensitivity analyses.I2and Q value statistics were used to appraise the heterogeneity among genetic variants.In univariable analysis, genetic liability to insomnia was significantly associated with worse functional outcome (modified Rankin Scale ≥3) after ischemic stroke (OR = 1.30; 95% CI: 1.10-1.54,P= 0.002). Genetic liability to short sleep, long sleep and continuous sleep duration were not associated with post-stroke functional outcome (allP> 0.05). Sensitivity analyses without adjustment for stroke severity also supported that insomnia was causally associated with poor functional outcome (OR = 1.25; 95% CI: 1.08-1.44,P= 0.003). In the multivariable MR analysis adjusting for potentially confounding traits including body mass index, depression, type 2 diabetes, smoking and alcohol consumption, the overall patterns between genetic liability to insomnia and post-stroke outcome remained (allP< 0.05).The present MR study supports potential adverse effects of liability to insomnia on functional outcome after ischemic stroke. Interventions that address insomnia may offer a therapeutic target to improve recovery after ischemic stroke, and warrant exploration in a clinical context.