Complex Causal Association between Immunophenotypes and Adenomyosis: univariable, bidirectional, and multivariable Mendelian randomization

This study aimed to explore the causal link between immunophenotypes and adenomyosis using Mendelian randomization (MR). We conducted a bidirectional MR analysis on 731 immunophenotypes, employing inverse-variance weighted (IVW) as the primary method, supplemented by MR-Egger, weighted mode, and weighted median analyses. Sensitivity analyses were performed to ensure result robustness. Multivariable MR was also used to control for confounding among immune cells. Results showed that 16 immunophenotypes were positively associated with adenomyosis (p < 0.05, OR > 1), while 10 had a negative correlation (p < 0.05, OR < 1). Reverse MR revealed 16 positive and 4 negative correlations with adenomyosis (P < 0.05, OR > 1 or < 1). Multivariable MR identified 5 risk factors and 8 protective factors for adenomyosis (P < 0.05, OR > 1 or < 1). This study clarifies the significant correlation between immune cells and adenomyosis, offering valuable insights for future clinical research.