Mendelian randomization analysis of the causal links between immune cells, metabolites, and ectopic pregnancy

Ectopic pregnancy (EP) is a severe medical condition with uncertain etiological determinants. This study seeks to examine the causal associations among immune cell phenotypes, metabolites, and EP susceptibility through Mendelian Randomization (MR) analysis. Genetic data on immune cell traits and metabolites were obtained from publicly accessible GWAS datasets, encompassing 7,824 participants from the TwinsUK and KORA cohorts. A bidirectional MR approach was employed to assess genetic correlations between immune cells, metabolites, and EP risk.We identified several immune cell phenotypes, such as CD45RA + CD28- CD8br AC, which showed a significant inverse relationship with EP risk. Additionally, multiple metabolites, including Dibutyl sulfosuccinate, N-acetyl-L-alanine, and Beta-hydroxyisovalerate, were positively associated with EP risk. Mediation analysis revealed that immune cell phenotypes, particularly CD28- CD8dim %CD8dim, influenced EP risk through metabolites like Dibutyl sulfosuccinate, suggesting a regulatory interaction. Sensitivity analyses using various MR methods confirmed the robustness of the findings. These results indicate that immune cell phenotypes and metabolites play a significant role in the pathogenesis of EP, providing novel insights into potential biomarkers for EP risk and opening new avenues for targeted interventions.