Genetic insights into the relationship between immune cell traits and abnormal uterine bleeding: A Mendelian randomization study

Abnormal uterine bleeding (AUB) is an inflammatory response involving immune cells, but the relationship between immune cell traits and AUB is highly complex and still largely unclear. This study utilized genetic data from a genome-wide association study of European participants. Mendelian randomization (MR) analysis methods, including inverse variance weighted (IVW) as the primary approach, weighted median, MR Egger regression, and Mendelian randomization pleiotropy residual sum and outlier, were employed for forward and reverse analyses. Sensitivity analyses validated the stability and reliability of the results. The IVW method indicated a potential causal relationship between CD45 on granulocyte (odds ratio [OR] = 0.916, 95% CI: 0.880-0.954, P = 1.974 × 10-5) with a decreased risk of menorrhagia. Two immune cell traits with P values < .001 were worthy of attention, CD25 on naive-mature B cell (OR = 0.935, 95% CI: 0.901-0.970, P = 3.882 × 10-4) may be associated with a decreased risk of menorrhagia, while human leukocyte antigen DR on plasmacytoid dendritic cell (OR = 1.089, 95% CI: 1.038-1.143, P = 5.126 × 10-4) may be associated with an increased risk of amenorrhea. No reverse causation was observed. Sensitivity analysis suggested no heterogeneity or horizontal pleiotropy (P > .05). No immune cell traits associated with or potentially related to oligomenorrhea were found. This MR study highlights the complex relationship between immune cell traits and AUB, offering insights into AUB's pathogenesis and potential biomarkers. Further clinical and in vitro validation is needed to assess these findings, with future research exploring immune modulation therapies for early diagnosis and personalized treatment.