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

Area of Science:

• Immunology and Genetics
• Reproductive Health

Background:

• Uterine fibroids (UF) are common benign tumors affecting women of reproductive age.
• The underlying causes and pathogenesis of UF remain incompletely understood.
• The role of immune system dysregulation in UF development requires further investigation.

Purpose of the Study:

• To investigate potential two-way causal associations between immune cell phenotypes and uterine fibroids (UF) using a bidirectional Mendelian randomization (MR) framework.
• To identify specific immune cell types that causally influence the risk or development of UF.
• To explore whether UF causally affects immune cell phenotypes.

Main Methods:

• Utilized a bidirectional Mendelian randomization (MR) framework.
• Employed large-scale genome-wide association study (GWAS) data for 731 immune cell phenotypes and UF.
• Applied inverse-variance weighted (IVW) method for primary analysis, with MR-Egger, weighted median, MR-PRESSO, leave-one-out, and false discovery rate (FDR) correction for sensitivity and validation.

Main Results:

• Forward MR identified 39 immune phenotypes associated with UF (23 risk, 16 protective).
• Three immune phenotypes showed strong potential causal links with UF: CD39⁺ CD8⁺ T cells, CD25 expression on IgD⁻ CD27⁻ B cells, and HLA-DR expression on CD14⁺ CD16⁻ monocytes.
• Reverse MR suggested UF may negatively impact the proportion of CD39⁺ CD8⁺ T cells, though this did not remain significant after FDR correction.

Conclusions:

• Provides genetic evidence for a forward causal link between specific immune cell phenotypes and UF.
• Suggests a potential reverse causal effect of UF on CD39⁺ CD8⁺ T cells.
• Highlights the importance of immune regulation in the pathogenesis of uterine fibroids.