基于两样本双向孟德尔随机化方法分析慢性心力衰竭与记忆力减退的因果关系  

Analysis of the causal relationship between chronic heart failure and memory impairment based on two sample bidirectional Mendelian randomization method

作　　者：赵雪莲 王少卿[2] 杨涛[2] 赵雪松[2] ZHAO Xuelian;WANG Shaoqing;YANG Tao;ZHAO Xuesong(Department of Gastroenterology,Dongfang Hospital,Beijing University of Chinese Medicine,Beijing100072,China;Department of Traditional Chinese Medicine,Beijing Tiantan Hospital,Capital Medical University,Beijing100070,China)

机构地区：[1]北京中医药大学东方医院消化科,北京100072 [2]首都医科大学附属北京天坛医院中医科,北京100070

出　　处：《中国医药导报》2024年第35期21-28,共8页China Medical Herald

摘　　要：目的 采用两样本孟德尔随机化(MR)分析探讨慢性心力衰竭与记忆力减退的因果关系。方法 从IEU OPEN GWAS PROJECT数据库下载慢性心力衰竭和记忆力减退的GWAS数据,暴露因素为慢性心力衰竭,结局指标为记忆力减退,提取合格的单核苷酸多态性(SNP)作为工具变量。采用的主要统计方法为逆方差加权法(IVW),同时以MR-Egger回归法、加权模式法、加权中位数法、简单模式法对IVW分析结果进行补充,采用Cochran’s Q检验判断SNP间的统计学异质性,采用MR-Egger回归法的截距项评估SNP是否存在水平多效性,采用留一法评估单个SNP对IVW分析结果的影响。为避免反向因果关系,将记忆力减退作为暴露因素,慢性心力衰竭作为结局指标,进行反向孟德尔随机化分析。结果 本研究共筛选出7个与慢性心力衰竭强相关的SNPs,剔除回文序列2个SNPs,最终纳入5个与慢性心力衰竭强相关的SNPs。IVW分析结果 (OR=0.56,95%CI:0.34~0.92,P=0.021)显示慢性心力衰竭会增加记忆力减退的发病风险,虽然MR-Egger回归法(OR=0.64,95%CI:0.19~2.18,P=0.528)、加权中位数法(OR=0.76,95%CI:0.40~1.45,P=0.383)、简单模式法(OR=0.81,95%CI:0.32~2.03,P=0.692)和加权模式法(OR=0.79,95%CI:0.33~1.90,P=0.664)分析结果显示慢性心力衰竭不会增加记忆力减退的发病风险,但其β值与IVW的β值方向一致。Cochran’s Q检验和提示所得结果稳健且不存在异质性(P=0.432),MR-Egger回归法的截距评估提示结果稳定,不存在水平多效性(P=0.820)。反向MR分析发现,暴露因素记忆力减退与结局慢性心力衰竭不存在因果关系(OR=1.00,95%CI:0.99~1.03,P=0.507)。结论 慢性心力衰竭会增加记忆力减退的发病风险。Objective To investigate the causal relationship between chronic heart failure and memory impairment by using two sample Mendelian randomization(MR)analysis.Methods GWAS data of chronic heart failure and memory impairment were downloaded from IEU OPEN GWAS PROJECT database.The exposure factor was chronic heart failure and the outcome indicator was memory impairment.Qualified single nucleotide polymorphism(SNP)was extracted as instrumental variables.The main statistical method used was inverse variance weighted(IVW).Meanwhile,MR-Egger regression method,weighted model method,weighted median method,and simple model method were used for supplementary test analysis of the IVW analysis results.Cochran’s Q test was used to determine the statistical heterogeneity among SNPs.The intercept term of MR-Egger regression method was used to evaluate whether there was horizontal pleiotropy of SNP,and the influence of single SNP on IVW analysis results was evaluated by leave-one method.In order to avoid reverse causality,memory impairment as the exposure factor and chronic heart failure as the outcome indicator were analyzed by reverse Mendelian randomization.Results In this study,seven SNPs strongly associated with chronic heart failure were screened out,two SNPs in the palindromic sequence were excluded,and five SNPs strongly associated with chronic heart failure were finally included.IVW analysis results(OR=0.56,95%CI:0.34-0.92,P=0.021)showed that chronic heart failure could increase the risk of memory impairment,although MR-Egger regression method(OR=0.64,95%CI:0.19-2.18,P=0.528),weighted median method(OR=0.76,95%CI:0.40-1.45,P=0.383),simple model method(OR=0.81,95%CI:0.32-2.03,P=0.692)and weighted model method(OR=0.79,95%CI:0.33-1.90,P=0.664)analysis showed that chronic heart failure did not increase the risk of memory loss,but itsβvalues were consistent with those of IVW.The results obtained by Cochran’s Q test and suggestion were robust with no heterogeneity(P=0.432),and the intercept evaluation of MR-Egger regression

关 键 词：慢性心力衰竭 记忆力减退 孟德尔随机化 因果关联 

分 类 号：R25[医药卫生—中医内科学]