基于孟德尔随机化的类风湿性关节炎及其血清抗体水平与子痫前期的因果关系分析  

Analysis on causal relationship between rheumatoid arthritis andits serological antibodies levels with pre-eclampsia basedon Mendelian randomization

作　　者：缪嘉燕[1] 钱雅婷 王一枭 薛璇[1] MIAO Jiayan;QIAN Yating;WANG Yixiao;XUE Xuan(Department of Obstetrics and Gynecology,Women’s Hospital of Nanjing Medical University/Nanjing Women and Children’s Healthcare Hospital,Nanjing,Jiangsu 210004,China)

机构地区：[1]南京医科大学附属妇产医院/南京市妇幼保健院妇产科,南京210004

出　　处：《重庆医学》2024年第9期1289-1294,共6页Chongqing medicine

基　　金：国家自然科学基金项目(82001546)。

摘　　要：目的基于孟德尔随机化(MR)探究类风湿性关节炎(RA)及其血清抗体水平与子痫前期(PE)的遗传因果关系。方法筛选显著差异的单核苷酸多态性(SNP)作为工具变量,应用以逆方差加权法(IVW)为主要分析方法的5种MR分析方法综合评估RA及其血清抗体水平与PE的因果关系。使用MR-Egger截距法、MR-多效性残差和异常值法、Cochrane’s Q检验评估SNP的水平多效性和异质性,使用留一法评估单个SNP对MR结果的影响。结果IVW分析结果表明RA(OR=1.098,95%CI:1.036~1.164,P=0.002)和血清抗体阳性RA(OR=1.088,95%CI:1.026~1.153,P=0.005)是PE的危险因素,而血清抗体阴性RA(OR=1.036,95%CI:0.971~1.104,P=0.282)与PE之间不存在明显的因果关系。3种暴露因素的MR分析中使用的SNPs均未发现明显的水平多效性和异质性。rs34434863在RA、血清抗体阳性RA与PE的因果关系中发挥决定性作用。结论基于MR分析得出,RA、血清抗体阳性RA与PE之间存在明显的正向因果关系,而血清抗体阴性RA与PE之间不存在明显的因果关系。Objective To investigate the genetic causal relationship between rheumatoid arthritis(RA)and its serological antibody levels with pre-eclampsia(PE)based on Mendelian randomization(MR).Methods Single nucleotide polymorphism(SNP)with significant differences were screened as instrumental variables,and the five MR analytic method with the inverse variance weighting(IVW)as the main analytical method were applied to comprehensively assess the causal cc relationship between OA,serum antibody levels PE.The MR-Egger intercept method,MR pleiotropy residual and outlier(MR-PRESSO)method,Cochrane’s Q-test were applied to explore the horizontal pleiotropy and heterogeneity of SNP,and the leave-one-out method was used to explore the effect of individual SNPs on MR results.Results The IVW result indicated that RA(OR=1.098,95%CI:1.036-1.164,P=0.002)and seropositive RA(OR=1.088,95%CI:1.026-1.153,P=0.005)were the PE risk factors,whereas seronegative RA(OR=1.036,95%CI:0.971-1.104,P=0.282)did not have a significant causal relationship with PE.No significant level pleiotropy or heterogeneity was found in the SNPs used in MR analyses of the 3 exposure factors.rs34434863 played a decisive role in the causal relationship of RA and seropositive RA with PE.Conclusion Based on MR analysis,there is a significant positive causal relationship between RA and seropositive RA with PE,whereas there was no significant causal relationship between seronegative RA and PE.

关 键 词：类风湿性关节炎 血清学抗体 子痫前期 孟德尔随机化 因果关系 

分 类 号：R593.22[医药卫生—内科学]