Genetically Predicted Sleep Traits and Functional Outcome After Ischemic Stroke

Objective:

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.

Methods:

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. I² and Q value statistics were used to appraise the heterogeneity among genetic variants.

Results:

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 (all P > 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 (all P < 0.05).

Conclusions:

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.