Genetically predicted cycling-related behaviors and erectile dysfunction: a two-sample Mendelian randomization study

Background: Observational studies have reported inconsistent associations between cycling and erectile dysfunction (ED). Methods: Genome-wide association study (GWAS) summary data for cycling-related exposures were obtained from the Integrative Epidemiology Unit (IEU) OpenGWAS database, specifically for bicycle commuting to work and cycling excluding work. GWAS summary data for ED were obtained from the European Bioinformatics Institute (EBI) database. Independent single-nucleotide polymorphisms (SNPs) associated with cycling-related exposures were selected as instrumental variables. The inverse-variance weighted method was used as the primary Mendelian randomization (MR) analysis, whereas MR-Egger, weighted median, weighted mode, and simple mode methods were used as complementary analyses. Heterogeneity, horizontal pleiotropy, outliers, and the robustness of the findings were assessed using Cochran’s Q test, MR-Egger intercept test, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), and leave-one-out analysis, respectively. Results: For bicycle commuting to work, 30 SNPs were included as instrumental variables. The primary MR analysis showed no statistically significant evidence of a causal association between bicycle commuting to work and ED risk (odds ratio (OR) = 0.216, 95% confidence interval (CI): 0.034–1.389, p = 0.107). For cycling excluding work, 28 SNPs were included, and no statistically significant causal association with ED risk was observed (OR = 0.127, 95% CI: 0.012–1.385, p = 0.090). Sensitivity analyses indicated no substantial heterogeneity or directional horizontal pleiotropy, and leave-one-out analysis did not identify any single SNP that materially influenced the estimates. Conclusions: This two-sample MR study found no statistically significant evidence of a causal association between genetically predicted cycling-related behaviors and ED risk. However, given the wide confidence intervals, limited statistical power, potential sample overlap, and use of a relaxed SNP-selection threshold, these findings should be interpreted cautiously and warrant further validation.

Erectile dysfunction; Male sexual dysfunction; Bicycle riding; Aerobic exercise; Mendelian randomization

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