Walking For Pleasure Associated With Stroke: A Two Sample Mendelian Randomization Study

Stroke is the world's second leading cause of death. In the elderly,it significantly impairs daily living abilities. Research suggests that moderate exercise can effectively reduce the risk of stroke.Due to the gradual decline in physical function,walking, being a simple and adaptable exercise, is a primary choice for the elderly.However,the specific relationship between walking as an exercise and the risk of stroke remains unclear. PURPOSE: This study utilizes a two-sample Mendelian Randomization approach to assess the causal relationship between walking for pleasure and stroke. METHODS: We sourced single-nucleotide polymorphisms (SNPs) as instrumental variables from European ancestry genome-wide association studies on stroke (6925 cases, 477673 controls) and walking for pleasure (460376 UK Biobank participants). We selected SNPs meeting specific criteria: strong association with the exposure variable (P < 5 × 10^-8), low linkage disequilibrium (r2 ≤ 0.001),and exclusion of weak instrumental variables based on the F-statistic threshold.Outliers were further excluded using the MR-PRESSO method.we ultimately selected 20 SNPs as instrumental variables.The analysis was primarily conducted using the IVW method,assessing results based on the odds ratio (OR) and 95% confidence interval (CI).The robustness and reliability of the results were further validated using the leave-one-out method,heterogeneity tests,and horizontal pleiotropy tests. RESULTS: In the IVW estimation, we found a negative correlation between the frequency of walking for pleasure and the risk of stroke (OR) of 0.903 (95% CI: 0.850-0.948, P = 0.001).Additionally,no horizontal pleiotropy was detected in the instrumental variables (MR-Egger intercept = 0.0017,P > 0.05).Significant heterogeneity among the instrumental variables was revealed through Cochran's Q test (Cochran's Q = 29.88, P = 0.039 < 0.05).The leave-one-out sensitivity analysis,which examines the impact of the remaining SNPs after excluding each individual SNP,did not identify any outlier SNPs or SNPs that significantly influence the results. CONCLUSION: Our study results confirm a significant causal relationship between walking and stroke,ecommending it as an effective exercise for older adults.