Relationships Between Accelerometer-measured and Multiple Sclerosis: a 2-sample Mendelian Randomization Study

Background: Observational studies suggest that physical activity (PA) can independently modify the risk of developing multiple sclerosis (MS).

Objective: To investigate the causal effect of PA on MS by Mendelian randomization (MR) approaches.

Methods: Through a genome-wide association study including 91,105 participants from UK Biobank, we obtained 5 single-nucleotide polymorphisms (SNPs) associated with accelerometer-measured PA (P < 5 × 10). Summary-level data for MS were obtained from a meta-analysis, incorporating 14,802 subjects with MS and 26,703 healthy controls of European ancestry. MR analyses were performed using the inverse-variance-weighted method, weighted median estimator, and MR-PRESSO method. Additional analyses were further performed using MR-Egger intercept and Cochran's Q statistic to verify the robustness of our findings.

Results: We failed to detect a causal effect of PA on MS (OR, 0.60; 95% confidence interval [CI], 0.30-1.20; P = 0.15) per in the random-effects IVW analysis. Additional MR methods yielded consistent results. MR-Egger regression suggested no evidence of horizontal pleiotropy (Intercept = 0.14, P = 0.21) and there seemed no substantial heterogeneity (I = 29.8%, P = 0.22) among individual SNPs.

Conclusion: Our findings suggest that enhancing PA might not modify the risk of developing MS independent of established risk factors.