Increased walking pace reduces the rate of erectile dysfunction: results from a multivariable Mendelian randomization study

Abstract Background Previous observational studies have identified a potential association between walking and the risk of erectile dysfunction (ED); however, the causal relationship between them remains unclear. Aim This study aims to explore the causal relationship between walking and ED using Mendelian randomization (MR). Methods MR analysis was conducted using genome-wide association study (GWAS) data related to walking pace. The inverse variance weighted (IVW) method was used as the primary MR analysis method. To supplement the IVW results, two additional MR methods were used: MR-Egger and weighted median (WM). Sensitivity analyses were performed to assess heterogeneity and pleiotropy. Furthermore, multivariable MR (MVMR) analysis was employed to evaluate the causal relationship after adjusting for potential confounding factors. Outcomes The moderating effects of different walking phenotypes on ED. Results According to the IVW method, genetically predicted walking pace was found to have a reverse causal relationship with the risk of ED (OR: 0.24; 95% CI: 0.12-0.51). Similar causal effects were observed using the other two MR methods, with statistical significance found in the WM method and validation through sensitivity analyses. Furthermore, MVMR analysis confirmed that the protective effect of increased walking pace on reducing the risk of ED remained significant even after adjusting for potential confounders. Clinical Implications Encouraging men to engage in brisk walking could be an effective strategy for reducing the incidence of ED. Strengths and Limitations This study utilized large-scale GWAS summary data on walking and ED and employed a two-sample, multivariable MR design to minimize confounding factors and reverse causation, enabling the derivation of credible causal effects. It is essential to obtain GWAS data from other populations and replicate this MR analysis to validate the results, as well as conduct further research to explore the underlying mechanisms. Conclusion The results of this study suggest that there is an inverse causal relationship between walking pace and ED risk, and brisk walking may be an independent protective factor against ED.