Genetic associations between physical activity levels and functional outcome after ischemic stroke: Insights from Mendelian randomization

Objective

The genetic relationship between daily physical activity (PA) levels and functional outcome after ischemic stroke remains unclear. This study aimed to investigate the genetic associations of PA on functional outcome after ischemic stroke using Mendelian randomization (MR).

Methods

We conducted two-sample MR analyses using genome-wide association studies (GWASs). This included data on light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) from the UK Biobank, and functional outcome after ischemic stroke from the Genetics of ischemic stroke Functional Outcome (GISCOME). The inverse-variance weighted (IVW) method served as our primary MR analysis approach, supplemented by several sensitivity analyses.

Results

In univariable Mendelian randomization (UVMR) analysis, MVPA was significantly associated with a reduced risk of poor functional outcome (OR = 0.15, 95 % CI = 0.04–0.56, P < 0.01), whereas LPA had no genetic relationship (OR = 0.37, 95 % CI = 0.002–51.40, P = 0.69). In multivariate Mendelian randomization (MVMR) analysis adjusting for potentially confounding traits including hypertension, type 2 diabetes, and smoking, the overall patterns between MVPA and poststroke outcome remained (OR = 0.23, 95 % CI = 0.07–0.78, P = 0.02).

Conclusion

MVPA is a protective factor for functional outcome after ischemic stroke. This finding is important for the rehabilitation and functional outcome of stroke patients.