腰围与扩张型心肌病的因果关系:双向两样本孟德尔随机化分析

Causal Relationship between Waist Circumference and Dilated Cardiomyopathy:a Two-Way Two-Sample Mendelian Randomization Analysis

目的基于双向两样本孟德尔随机化(MR)分析方法探讨腰围与扩张型心肌病(DCM)的因果关系。方法2023-12-20,从IEU OpenGWAS project网站获取腰围数据集和DCM数据集,其均为欧洲人群样本,其中腰围数据集的样本量为462166例、单核苷酸多态性(SNP)数量为9851867个;DCM数据集的样本量为355381例,SNP数量为19080278个。本研究以逆方差加权法(IVW)分析结果为主,以加权中位数法(WME)、MR-Egger回归、简单模型、加权模型分析结果为补充,以SNP为工具变量,分析腰围与DCM的因果关系。使用Cochran Q检验判断SNP间是否存在统计学异质性,采用MR-Egger回归的截距项、MR-PRESSO检验分析SNP的水平多效性,使用留一法分析单个SNP对IVW分析结果的影响,绘制漏斗图以评估SNP的潜在偏倚。结果本研究最终纳入348个与腰围强相关的SNP,14个与DCM强相关的SNP。IVW分析结果显示,腰围增加是DCM的危险因素〔OR=2.046,95%CI(1.548~2.703),P<0.01〕;WME分析结果显示,腰围增加是DCM的危险因素〔OR=1.892,95%CI(1.257~2.848),P<0.01〕;MR-Egger回归、简单模型、加权模型分析结果显示,腰围增加不是DCM的危险因素(P>0.05),但其β值与IVW的β值方向一致。IVW、WME、MR-Egger回归、简单模型、加权模型分析结果均显示,DCM与腰围无因果关系(P>0.05)。Cochran Q检验结果显示,与腰围、DCM强相关的SNP间均不存在统计学异质性(P>0.05)。MR-Egger回归的截距项、MR-PRESSO检验结果均显示,与腰围、DCM强相关的SNP均无水平多效性(P>0.05)。留一法分析结果显示,逐一剔除单个与腰围、DCM强相关的SNP后,IVW分析结果均无明显改变。漏斗图分析结果显示,与腰围、DCM强相关的SNP基本对称分布,无潜在偏倚。结论腰围增加是DCM的危险因素。

Objective To explore the causal relationship between waist circumference and dilated cardiomyopathy(DCM)based on two-way two-sample Mendelian randomization(MR)analysis method.Methods 2023-12-20,the waist circumference data set and DCM data set were obtained from the IEU OpenGWAS project website,all of which were European samples.The sample size of the waist circumference data set was 462166,and the number of single nucleotide polymorphisms(SNP)was 9851867.The sample size of DCM data set was 355381,and the number of SNP was 19080278.This study was mainly based on the results of inverse variance weighting(IVW)analysis,supplemented by the results of weighted median estimator(WME),MR-Egger regression,simple model and weighted model analysis.SNP was used as an instrumental variable to analyze the causal relationship between waist circumference and DCM.CochranQtest was used to determine whether there was statistical heterogeneity among SNPs.The intercept term of MR-Egger regression and MR-PRESSO test were used to analyze the level pleiotropy of SNPs.The effect of a single SNP on the results of IVW analysis was analyzed using the leave-one-out method.Funnel plot was drawn to evaluate the potential bias of SNP.Results Finally,348 SNPs strongly associated with waist circumference and 14 SNPs strongly associated with DCM were included in this study.The results of IVW analysis showed that increased waist circumference was a risk factor for DCM[OR=2.046,95%CI(1.548-2.703),P<0.01].WME analysis showed that increased waist circumference was a risk factor for DCM[OR=1.892,95%CI(1.257-2.848),P<0.01].The results of MR-Egger regression,simple model and weighted model analysis showed that the increase of waist circumference was not a risk factor for DCM(P>0.05),but theirβvalues were consistent with the direction ofβvalue of IVW.The results of IVW,WME,MR-Egger regression,simple model and weighted model analysis showed that there was no causal relationship between DCM and waist circumference(P>0.05).CochranQtest results showed that there was no statistical heterogeneity among SNPs strongly associated with waist circumference and DCM(P>0.05).The results of the intercept term of MR-Egger regression and MR-PRESSO test analysis showed that there was no horizontal pleiotropy of SNPs strongly associated with waist circumference and DCM(P>0.05).The results of the leave-one-out analysis showed that there was no significant change in the IVW analysis results after the single SNP strongly related to waist circumference and DCM was removed one by one.The results of funnel plot analysis showed that the SNPs strongly correlated with waist circumference and DCM were basically symmetrically distributed,and without potential bias.Conclusion Increased waist circumference is a risk factor for DCM.