Bidirectional Mendelian Randomization Reveals Causal Effects of Immune Cell Traits on Endometriosis Risk

ABSTRACT Purpose Previous studies have identified associations between immune cell traits and endometriosis, but the causality of these relationships remains uncertain. In this study, we utilized Mendelian randomization (MR) to investigate the causal relationship between immune cell traits and endometriosis for the first time. Methods Seven hundred and thirty‐one immune cell signatures associated with single‐nucleotide polymorphisms (SNPs) were extracted from a published genome‐wide association study (GWAS) involving 472 174 individuals, while endometriosis data, including four stages and seven subtypes, were obtained from the FinnGen consortium. Four methods were used for MR. The causal effect of immune cell traits on endometriosis was explored after Bonferroni correction. Results Significant causal relationship included 92 immune cell traits distributed among B cell (28 cells), cDC (2 cells), maturation stages of T cell (10 cells), monocyte (12 cells), Myeloid cell (5 cells), TBNK (13 cells), and Treg panels (22 cells). One of the most significant findings is that for every 1‐standard deviation (SD) increase in CD8 on Central Memory CD8 + T cell, the risks of developing endometriosis of the fallopian tube increased by 72%. In the reverse MR analysis, a one‐unit increase in the log odds of endometriosis of the ovary risk corresponded to a decrease in the absolute count of CD4 + CD8 dim T cell by 0.10. Conclusion This study represents the first comprehensive evaluation of the causal effects of immune cell traits on the risk/protection of different stages/subtypes of endometriosis. The findings highlight the complex and significant role of immune‐derived factors in the pathogenesis of the disease.