基于孟德尔随机化探究免疫细胞和女性不孕症的因果关联  

Causal role of immune cells in female infertility:Mendelian randomization(MR)study

作　　者：罗嘉玲 王道远 毛珮琪 夏梦鸽 甘甜 李艳青[2] LUO Jialing;WANG Daoyuan;MAO Peiqi;XIA Mengge;GAN Tian;LI Yanqing(The Second Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou,Henan 450003,China;Henan Province Hospital of TCM,Zhengzhou,Henan 450003,China)

机构地区：[1]河南中医药大学第二临床医学院,河南郑州450003 [2]河南省中医院,河南郑州450003

出　　处：《中国优生与遗传杂志》2024年第5期904-910,共7页Chinese Journal of Birth Health & Heredity

基　　金：河南省重点研发与推广专项(科技攻关)(222102310202);河南省中医药科学研究专项课题(2022ZY2015)。

摘　　要：背景先前的研究已经观察到免疫细胞与女性不孕症之间的关联,但研究得出了不一致的结果,免疫细胞与女性不孕症之间的因果关联仍未确定。方法根据公开的全基因组关联研究(GWAS)汇总统计数据,本研究进行了两样本孟德尔随机化(MR)来评估731种免疫表型与女性不孕症之间的因果关联。除此之外,本研究还识别和量化了炎症蛋白作为潜在介质的作用。本研究以逆方差加权(IVW)作为主要分析方法,以MR-Egger回归、加权中位数法(weighted median)、简单模型(simple mode)、加权模型(weighted mode)等方法作为IVW结果的补充证据,同时进行水平多效性和异质性检验以确保结果的稳定性。结果FDR校正后(P<0.05),发现1种免疫表型与女性不孕症风险显著相关:CD4 on activated&secreting Treg(OR=0.92,95%CI:0.89~0.96,P=1.70×10^(-5),P_(FDR)=0.012)。通过对中介因素的探索,观察到1种可能存在中介作用的炎症蛋白:Interleukin-15 receptor subunit alpha levels(中介效应占比:4.9%,95%CI:4.7%~5.1%)。结论本研究通过遗传手段证明了免疫细胞与女性不孕症之间的因果关联,并发现1种炎症蛋白可能具有潜在的介导作用,为从免疫学角度制定更为个体化和有效的预防与治疗方案提供了新的研究方向。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),P_(FDR)=0.012).Through the exploration of mediating factors,this study observed 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.

关 键 词：女性不孕症 免疫 炎症蛋白 孟德尔随机化 

分 类 号：R711.6[医药卫生—妇产科学]