Abstract
Atorvastatin, a common cardiovascular drug, lowers cholesterol but its link to erectile dysfunction (ED) risk is unclear. This study uses a two-sample MR approach to clarify this. This study used three GWAS datasets: one for atorvastatin use (13851 cases, 449082 controls), and two for ED in Europeans (6175 cases, 217630 controls; 357 cases, 208451 controls). Two MR analyses assessed atorvastatin as exposure and ED as outcome, using IVW, MR Egger et al.. Meta-analysis improved result reliability. MR-Presso global test and MR-Egger assessed pleiotropy, while co-localization analyzed shared genetic factors. One set of MR analysis results did not find evidence supporting a causal relationship between the two variables. However, the IVW results from another set (OR = 1.992, 95% CI = 1.138 ~ 3.489, P = 0.016) and the final meta-analysis (P = 0.010) both indicated a potential association between atorvastatin use and ED. Sensitivity analysis did not detect pleiotropy or heterogeneity, and leave-one-out analysis showed no significant influence from instrumental variables. Additionally, co-localization analysis revealed no shared genetic factors between atorvastatin use and ED, suggesting a direct impact of exposure on the outcome. This study's results show a potential link between atorvastatin use and ED, suggesting increased ED risk for users.