尿酸介导体重指数与慢性心力衰竭关系的孟德尔随机化分析  

Mendelian Randomization Analysis on the Causal Association Between Uric Acid-mediated Body Mass Index and Congestive Heart Failure

作　　者：葛腾 房瑛 齐鸿飞 宁博 吴永青 赵明君[1,4] GE Teng;FANG Ying;QI Hongfei;NING Bo;WU Yongqing;ZHAO Mingjun(Department of Clinical Medicine of Integrated Traditional Chinese and Western Medicine,The First Clinical Medical College,Shaanxi University of Chinese Medicine,Xianyang 712046,China;Emergency Center,The Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China;Shaanxi Key Laboratory of Integrated Traditional and Western Medicine for Prevention and Treatment of Cardiovascular Disease,Xianyang 712000,China;Department of Cardiology,The Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China)

机构地区：[1]陕西中医药大学第一临床医学院中西医临床医学系,咸阳712046 [2]陕西中医药大学附属医院急救中心,咸阳712000 [3]陕西省中西医结合心血管病防治重点实验室,咸阳712000 [4]陕西中医药大学附属医院心血管一科,咸阳712000

出　　处：《中国循环杂志》2024年第5期495-502,共8页Chinese Circulation Journal

基　　金：国家重点研发计划——中医药现代化研究重点专项(2018YFC1704204);名中医赵明君传承工作室建设项目(2019007);陕西省教育厅重点实验室项目(22JS005);陕西省自然科学基础研究计划一般项目——青年项目(2021JQ-738);陕西省高校科协青年人才托举计划项目(20200312)。

摘　　要：目的:采用两样本孟德尔随机化分析探讨体重指数、尿酸与慢性心力衰竭(CHF)之间的因果关系。方法:使用公开的东亚人群全基因组关联研究汇总数据集,以逆方差加权(IVW)法为主要分析方法,同时采用MR-Egger回归法、加权中位数模型、简单模型、加权模型,分析体重指数、尿酸与CHF两两之间的关系。使用MR-Egger回归法检测多效性,使用Cochran Q检验检测异质性,使用留一法进行敏感性分析,绘制漏斗图检测偏倚性,使用MR-PRESSO包剔除离群单核苷酸多态性(SNP)。孟德尔分析后计算中介效应值及中介效应比例,最后分析体重指数、尿酸与CHF两两之间的反向孟德尔随机化研究。结果:两样本孟德尔分析中IVW法显示体重指数(OR=1.685,95%CI:1.417~2.003,P<0.001)、尿酸(OR=1.225,95%CI:1.087~1.380,P<0.001)均与CHF存在因果关系;体重指数(OR=1.204,95%CI:1.139~1.273,P<0.001)与尿酸存在因果关系。尿酸在体重指数与CHF的因果关系中的中介效应比例为7.23%。MR-Egger回归截距的P均>0.05,即筛选出的SNP不存在水平多效性,因果推断方法有效,体重指数-尿酸、体重指数-CHF的孟德尔随机化分析存在异质性(Cochran Q检验P<0.01)。反向孟德尔随机化分析中IVW法显示,CHF与体重指数(OR=0.977,95%CI:0.947~1.008,P>0.05)、CHF与尿酸(OR=1.000,95%CI:0.963~1.038,P>0.05)之间均不存在因果关系,尿酸与体重指数的分析存在基因多效性,故因果推断方法无效。结论:体重指数、尿酸均与CHF存在因果关系且呈正相关,且尿酸在体重指数与CHF的因果关系中为不完全中介因素。Objectives:To explore the causal relationship between body mass index,uric acid and congestive heart failure(CHF),and provide genetic evidence to support the association between uric acid-mediated body mass index and the risk of CHF.Methods:Using the published data set of genome-wide association studies(GWAS)in East Asia,inverse variance weighting(IVW)method was used as the main analysis method,and MR-Egger method,weighted median model(WME),simple model and weighted model were used to analyze the causal relationship between body mass index,uric acid and CHF.MR-Egger regression was used to detect pleiotropy,Cochran Q test was used to detect heterogeneity,leave-one-out sensitivity was used to detect bias,funnel plot was drawn to detect bias,and MR-PRESSO package was used to remove outlier single nucleotide polymorphism(SNP).After Mendelian analysis,the mediating effect ratio was calculated,and the reverse Mendelian randomization study results between body mass index,uric acid and CHF were analyzed.Results:IVW method showed that body mass index(OR=1.685,95%CI:1.417-2.003,P<0.001)and uric acid(OR=1.225,95%CI:1.087-1.380,P<0.001)were risk factors of CHF in two-sample Mendelian analysis.Body mass index(OR=1.204,95%CI:1.139-1.273,P<0.001)was a risk factor for uric acid.The mediating effect of uric acid was 7.23%.The P values of MR-Egger regression intercept terms were all>0.05,that is,there was no pleiotropy of the selected SNP,and the causal inference method was valid.The Cochran Q test Pvalues of body mass index and uric acid,and body mass index and CHF were<0.01,indicating heterogeneity.IVW analysis of CHF and body mass index in reverse Mendelian analysis was OR=0.977,95%CI:0.947-1.008,P>0.05 and CHF and uric acid was OR=1.000,95%CI:0.963-1.038,P>0.05,so the reverse causal inference was not valid.However,the analysis of uric acid and body mass index showed pleiotropy,so the causal inference method was invalid.Conclusions:There is a causal and positive correlation between body mass index and CHF.There is a causal rela

关 键 词：体重指数 尿酸 慢性心力衰竭 孟德尔随机化分析 因果关系 中介效应 

分 类 号：R54[医药卫生—心血管疾病]