Objective: This research applied a bidirectional Mendelian randomization (MR) framework to investigate potential two-way causal associations between immune cell phenotypes and uterine fibroids (UF). Methods: This research drew upon publicly available data from large-scale genome-wide association studies (GWAS), encompassing 731 immune cell phenotypes from 3757 participants and UF data from 21,024 cases and 237,694 controls. Primary causal estimates were derived using the inverse-variance weighted (IVW) approach, with additional validation through MR-Egger, weighted median, and related methods. To ensure the reliability of the results, MR-PRESSO analysis, leave-one-out analysis, and false discovery rate (FDR) correction were also performed. Results: Forward MR analyses initially identified 39 immune phenotypes significantly associated with UF (IVW P 0.05—three phenotypes demonstrated strong causal links with UF: CD39⁺ CD8⁺ T cells, CD25 expression on IgD − CD27 − B cells, and HLA-DR expression on CD14⁺ CD16 − monocytes (all IVW P < 0.001). The reverse MR analysis indicated a negative causal effect of UF on the proportion of CD39⁺ CD8⁺ T cells (IVW OR = 0.895, P = 0.037). Sensitivity analyses ruled out interference from horizontal pleiotropy and heterogeneity, supporting the reliability of the study’s conclusions. However, after FDR correction, none of the causal associations remained statistically significant. Conclusion: Our research offers compelling genetic evidence supporting a forward causal link between CD39⁺ CD8⁺ T cells, CD25 on IgD − CD27 − B cells, and HLA-DR on CD14⁺ CD16 − monocytes and UF, and a reverse causal link between CD39⁺ CD8⁺ T cells and UF, highlighting immune regulation as a potentially pivotal factor in UF pathogenesis. Keywords: uterine fibroids, immune cells, bidirectional mendelian randomization, inverse-variance weighted, causality
Deng et al. (Wed,) studied this question.