A causal link between circulating immune cells and erectile dysfunction: Two-sample bidirectional Mendelian randomization study

Emerging observational studies have highlighted a robust association between circulating immune cells and erectile dysfunction (ED); however, these associations may be confounded by underlying factors. To elucidate this relationship, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis to evaluate the potential causal links between circulating immune cell and ED. Utilizing large-scale genetic datasets from publicly available sources, we systematically investigated causal associations across 731 distinct immunophenotypes and ED risk, supported by rigorous sensitivity analyses to ensure robustness, evaluate heterogeneity, and detect horizontal pleiotropy. In forward MR analyses, 28 immune phenotypes were identified as having a causal association with ED. Notably, 3 specific phenotypes: CD25 + resting Treg cells, CD33dim HLA-DR + CD11b + antigen-presenting cells, and CD3- lymphocyte antigen-presenting cells, exhibited consistent significance across multiple MR methods, including inverse-variance weighted, MR-Egger, and weighted median analyses. Additionally, reverse MR analyses revealed that ED could causally influence 41 immune phenotypes, with 11 phenotypes showing consistent significance across the same analytical approaches. These findings underscore the complex bidirectional relationship between circulating immune cells and ED, providing critical insights into ED pathogenesis and potential targets for novel therapeutic interventions.