Sarcopenia-related traits and erectile dysfunction: a bi-directional Mendelian randomization study

Abstract Background Erectile dysfunction (ED) and sarcopenia share many risk factors, but the causal direction of their association remains unclear. Aim To investigate the potential causal relationship between sarcopenia-related traits and ED using genetic data. Methods We conducted a bi-directional 2-sample Mendelian randomization (MR) analysis to evaluate the potential causal relationship between sarcopenia-related traits (hand grip strength, appendicular lean mass, and walking pace) and ED. We selected the inverse variance weighted (IVW) method as the main method to assess the causal effect, and we use Cochrane’s Q tests derived from the IVW and MR-Egger method to evaluate the heterogeneity. To investigate horizontal pleiotropy, the study employed MR-Egger and MR-PRESSO methods. Leave-one-out analysis was conducted to assess the influence of individual genetic loci on the outcomes. Outcomes Specific sarcopenia-related functional traits might increase the risk of ED, while reverse causality was not observed. Results When considering sarcopenia-related characteristics as exposure factors, we found a positive causal relationship between appendicular lean mass and ED (OR = 1.097, CI = 1.009-1.194, P = .029) and a negative causal relationship between walking pace and ED (OR = 0.325, CI = 0.172-0.613, P = .00052). Hand grip strength showed no causal relationship with ED. Reverse MR results indicated that ED as an exposure factor did not have a causal relationship with sarcopenia-related characteristics. The MR-Egger intercept indicated no evidence of horizontal pleiotropy (P > .05). Cochran’s Q test showed no significant heterogeneity (P > .05). Leave-one-out analysis revealed that excluding any single SNP did not significantly change the overall error lines, confirming the reliability of our conclusions. Clinical Implications Interventions aimed at improving overall physical function and fitness, particularly addressing a slow walking pace, may help reduce the risk of ED. Strengths and Limitations Key strengths include the MR design minimizing confounding and reverse causation, and comprehensive sensitivity analyses. The main limitation is that our study only contains samples of European descent. Conclusion Specific sarcopenia-related functional traits, particularly a slower walking pace, may play a causal role in ED. These findings highlight the importance of overall physical function and fitness in ED risk, although further studies are needed to clarify the specific role of muscle mass.