Causal role of immune cells in female infertility:Mendelian randomization(MR)study
Background Previous studies have observed associations between immune cells and female infertility,but results have been inconsistent,and the causal relationship between immune cells and female infertility remains uncertain.Methods Using publicly available summary statistics from genome-wide association study(GWAS),this study conducted a two-sample Mendelian randomization(MR)analysis to assess the causal relationship between 731 immune phenotypes and female infertility.Furthermore,the study identified and quantified the potential mediating role of inflammatory proteins.The primary analytical method was the inverse variance-weighted(IVW)approach,supplemented by MR-Egger regression,weighted median,simple mode,and weighted mode to provide additional evidence corroborating the IVW results.To ensure result stability,tests for horizontal pleiotropy and heterogeneity were performed.Results After FDR adjustment(P＜0.05),we identified one immune phenotype significantly associated with the risk of female infertility:CD4 on activated & secreting Treg(OR=0.92,95% CI:0.89-0.96,P=1.70×10-5,PFDR=0.012).Through the exploration of mediating factors,this study ob-served that interleukin-15 receptor subunit alpha levels may have a mediating effect,with a mediating effect of 4.9% (95% CI:4.7% -5.1% ).Conclusion This study found that immune cells and female infertility are causally associated.We also found that 1 inflammatory protein may have a potential mediating role.This finding provides new research directions for developing more personalized and effective prevention and treatment strategies from an immunological perspective.
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