Genetic evidence for causal effects of immune cell traits on risk for endometriosis: a bidirectional two-sample Mendelian Randomization Study

Abstract Previous studies have identified associations between immune cell traits and endometriosis, but the causality of these relationships remains uncertain. 731 immune cell signatures associated 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 Mendelian randomization. The causal effect of immune cell traits on endometriosis was explored after Bonferroni correction. 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). In the reverse Mendelian randomization 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+ CD8dim T cell by 0.10. 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.