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

Area of Science:

• Immunology
• Genetics
• Urology

Background:

• Observational studies suggest a link between immune cells and erectile dysfunction (ED).
• Potential confounding factors may affect these observed associations.
• Causal relationships require further investigation using robust methodologies.

Purpose of the Study:

• To investigate the potential causal relationship between circulating immune cell phenotypes and erectile dysfunction (ED).
• To explore the bidirectional causal associations between immune cells and ED using Mendelian randomization.

Main Methods:

• A two-sample Mendelian randomization (MR) analysis was performed.
• Utilized large-scale genetic data for 731 distinct immunophenotypes and ED risk.
• Employed rigorous sensitivity analyses (IVW, MR-Egger, weighted median) to ensure robustness and detect pleiotropy.

Main Results:

• Forward MR identified 28 immune phenotypes causally associated with ED.
• Three phenotypes (CD25+ resting Treg cells, CD33dim HLA-DR+ CD11b+ APCs, CD3- lymphocyte APCs) showed consistent significance.
• Reverse MR indicated ED causally influences 41 immune phenotypes, with 11 showing consistent significance.

Conclusions:

• A complex, bidirectional relationship exists between circulating immune cells and ED.
• Findings provide crucial insights into ED pathogenesis.
• Identified potential novel therapeutic targets for ED treatment.