The Relationship Between Immune Cells and Uterine Fibroids: A Bidirectional Mendelian Randomization Study

This research applied a bidirectional Mendelian randomization (MR) framework to investigate potential two-way causal associations between immune cell phenotypes and uterine fibroids (UF).

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.

Forward MR analyses initially identified 39 immune phenotypes significantly associated with UF (IVW P < 0.05), comprising 23 risk factors and 16 protective factors. Applying stringent selection criteria-IVW P < 0.001, consistent odds ratio (OR) directions across five analytical methods, and pleiotropy 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.

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.