Causal associations between sex hormones and keratoconus: a two-sample Mendelian randomization study

INTRODUCTION: This Mendelian randomization (MR) study evaluated potential causal associations between sex hormones and keratoconus (KC) using large-scale GWAS summary data. METHODS: The primary analysis utilized the inverse-variance weighted (IVW) method, supplemented by weighted median, MR-Egger regression, and Radial MR for outlier detection. Sensitivity analyses, including MR-PRESSO and leave-one-out tests, were performed alongside FDR correction to ensure robustness and control for multiple testing. Sensitivity analyses revealed no substantial heterogeneity or directional pleiotropy in the key models. DISCUSSION: In conclusion, these findings provide preliminary genetic evidence that testosterone-related pathways may influence KC development, particularly in males. However, as several findings remained nominal, they should be interpreted as hypothesis-generating rather than definitive and require further validation in future research.