盆腔炎性疾病和子宫内膜异位症之间的因果关系:一项两样本双向孟德尔随机化研究

Causal relationship between inflammatory pelvic disease and endometriosis:A two-sample bidirectional Mendelian randomization study

目的利用两样本双向孟德尔随机化(MR)分析盆腔炎性疾病(PID)与子宫内膜异位症(EMs)之间的潜在因果关系。方法从公开发表的全基因组关联数据库中筛选与PID和EMs有关的单核苷酸多态性(SNP)作为工具变量,双向分析均以逆方差加权法(IVW)分析为主,MR-Egger回归、加权中位数法(WME)、简单模型、加权模型作为补充,并运用Cochrane’sQ检验、MR-Egger截距法、MR-PRESSO、留一法等进行敏感性分析确保结果的稳健性。结果共筛选得到20个与PID相关的SNP,5个与EMs相关的SNP,正向孟德尔随机化IVW结果:OR=1.073,95%CI:1.005~1.146,P=0.033,且不存在异质性和水平多效性(P均>0.05),结果具有稳健性;反向MR分析IVW结果:OR=1.666,95%CI:1.215~2.283,P=1.493×10^(-3),异质性检验P均>0.05;MR-Egger、MR-PRESSO检验并剔除离群值后分析结果P>0.05,可证明不存在异质性和水平多效性。结论本研究从遗传学角度分析表明PID与EMs互为因果关系,可能具有相似的发病机制。

Objective To analyze the potential causal relationship between pelvic inflammatory disease(PID)and endometriosis(EMs)using two-sample bidirectional Mendelian randomization(MR).Methods Single nucleotide polymorphisms(SNPs)associated with PIDs and EMs were screened from publicly available genome-wide association databases as instrumental variables,and the two-way analyses were all based on inverse variance weighting(IVW)analysis,supplemented by MR-Egger regression,weighted median method(WME),simple model,and weighted model,and Cochrane’s Q test,MR-Egger intercept method,MR-PRESSO,and leave-one-out method for sensitivity analysis to ensure the robustness of the results.Results A total of 20 SNPs associated with PID and 5 SNPs associated with EMs were screened.The results of forward Mendelian randomization IVW:OR=1.073,95%CI:1.005-1.146,P=0.033,and there was no heterogeneity and horizontal pleiotropy(all P>0.05),and the results were robust.The results of reverse MR analysis IVW:OR=1.666,95%CI:1.215-2.283,P=1.493×10^(-3),and the P-values of the heterogeneity test were all>0.05.The P-values of the analysis results were>0.05 after the MR-Egger and MR-PRESSO tests and the exclusion of outliers,which can prove the absence of heterogeneity and horizontal pleiotropy.Conclusion Genetic analysis in this study showed that PID and EMs are causally related to each other and may have similar pathogenesis.