类风湿关节炎与肺栓塞的相关性:一项两样本孟德尔随机化研究  

The correlation between rheumatoid arthritis and pulmonary embolism: A two sample Mendelian randomization study

作　　者：韩玉艳 黄露露 杨梦妮 黄世红 黄艳 肖园园 李宏颖[2] 游运辉 HAN Yuyan;HUANG Lulu;YANG Mengni;HUANG Shihong;HUANG Yan;XIAO Yuanyuan;LI Hongying;YOU Yunhui(Department of Rheumatology and Immunology,Xiangya Changde Hospital,Changde 415000,Hunan,China;Department of Rheumatology and Immunology,the First Affiliated Hospital of Harbin Medical University,Harbin 150001,Heilongjiang,China)

机构地区：[1]湘雅常德医院风湿免疫科,湖南常德415000 [2]哈尔滨医科大学附属第一医院风湿免疫科,黑龙江哈尔滨150001

出　　处：《中国现代医生》2024年第7期13-16,25,共5页China Modern Doctor

基　　金：湖南省卫生健康委科研计划项目(202203105389);常德市科学技术局科技创新发展专项资金项目(2020S182)。

摘　　要：目的评估类风湿关节炎(rheumatoid arthritis,RA)与肺栓塞(pulmonary embolism,PE)的相关性。方法从大规模全基因组关联分析(genome wide association study,GWAS)获取研究数据,选择相互独立且与RA和PE相关的遗传位点作为工具变量。从GWAS中获取361194例RA患者和9704049名对照者、361194例PE患者和10721750名对照者数据。利用逆方差加权法(inverse variance weighted,IVW)、MR Egger、加权中位数法和加权模式进行两样本孟德尔随机化(Mendelian randomization,MR)分析,对RA与PE的相关性进行探讨。应用Cochran Q检验和孟德尔随机多态性残差和离群值(Mendelian randomization pleiotropy residual sum and outlier,MR-PRESSO)进行单核苷酸多态性(single nucleotide polymorphism,SNP)异质性评估。应用MR Egger截距测试检验SNP的水平多效性。利用“留一法”敏感度分析对MR研究是否受单个SNP的影响进行评价。结果IVW结果显示,RA可显著降低PE风险(β=–0.148,SE=0.063,P=0.018),且在加权中位数法及加权模式中被证实(β=–0.166,SE=0.051,P=0.001;β=–0.155,SE=0.054,P=0.045)。MR-PRESSO检测和MR Egger截距测试显示工具变量之间不存在异质性及水平多效性;“留一法”敏感度分析亦证实,无单个SNP对整体结果有较大影响。结论RA在遗传上与PE的风险降低有显著相关性。Objective To evaluate the correlation between rheumatoid arthritis(RA)and pulmonary embolism(PE).Methods Data were obtained from large-scale genome wide association study(GWAS),and independent genetic loci associated with RA and PE were selected as instrumental variables.Data were obtained from GWAS for 361194 patients with RA and 9704049 controls,361194 patients with PE and 10721750 controls.The inverse variance weighted(IVW),MR Egger,weighted median method and weighted model were used to conduct two sample Mendelian randomization(MR)analysis.Cochran Q test and Mendelian randomization pleiotropy residual sum and outlier(MR-PRESSO)were used to assess single nucleotide polymorphism(SNP)heterogeneity.Applying the MR Egger intercept to test horizontal pleiotropy of SNP.The sensitivity analysis of“leave one method”evaluated whether MR study was influenced by a single SNP.Results IVW results showed that RA could significantly reduce the risk of PE(β=-0.148,SE=0.063,P=0.018),and was confirmed in weighted median method and weighted model(β=-0.166,SE=0.051,P=0.001;β=-0.155,SE=0.054,P=0.045).The MR-PRESSO test and the MR Egger intercept test showed no heterogeneity or horizontal pleiotropy between instrumental variables.The sensitivity analysis of“leave one method”also confirmed that no single SNP had a significant impact on the overall results.Conclusion RA can significantly reduce the risk of PE in genetics.

关 键 词：类风湿关节炎 肺栓塞 孟德尔随机化 相关性 

分 类 号：R593.22[医药卫生—内科学]