甲状腺功能障碍与心力衰竭的因果关系:两样本孟德尔随机化分析  

Causal Relationship between Thyroid Dysfunction and Heart Failure:a Two-Sample Mendelian Randomization Analysis

作　　者：李仕康 曾浪 王坤 熊丽娟 崔扬扬 杜林芹 周阳 岳荣川[1,2] LI Shikang;ZENG Lang;WANG Kun;XIONG Lijuan;CUI Yangyang;DU Linqin;ZHOU Yang;YUE Rongchuan(Department of Cardiovascular Medicine,Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,China;Department of Cardiovascular Medicine,Guang'an Hospital,Affiliated Hospital of North Sichuan Medical College/Guang'an District People's Hospital,Guang'an 638550,China)

机构地区：[1]川北医学院附属医院心血管内科,四川省南充市637000 [2]川北医学院附属医院广安医院广安区人民医院心血管内科,四川省广安市638550

出　　处：《实用心脑肺血管病杂志》2024年第7期36-39,共4页Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease

基　　金：国家自然科学基金青年科学基金项目(81600232);四川省中央引导地方科技发展项目(2022ZYD0056);南充市2023年市级科技研发计划专项资金(23JCYJPT0059);川北医学院科研发展计划项目(CBY23-TD01)。

摘　　要：目的采用两样本孟德尔随机化(MR)分析探讨甲状腺功能障碍与心力衰竭(HF)的因果关系。方法采用两样本MR分析方法,通过IEU OpenGWAS prodect获取甲状腺功能亢进症数据集、甲状腺功能减退症数据集及HF数据集,其均来源于欧洲人群,其中甲状腺功能亢进症数据集样本量为460499例,单核苷酸多态性(SNP)数量为24189279个;甲状腺功能减退症数据集样本量为473703例,SNP数量为11973400个;HF数据集样本量为486160例,SNP数量为24178220个。以逆方差加权法(IVW)为主要MR分析方法,MR-Egger回归、加权中位数法(WM)、简单模型、加权模型为次要MR分析方法。采用Cochran's Q检验分析SNP间的统计学异质性,采用MR-Egger回归的截距项分析SNP的水平多效性,采用留一法分析单个SNP对MR分析结果的影响。结果IVW分析结果显示,甲状腺功能亢进症与HF风险增加相关〔OR=1.055,95%CI(1.016~1.095),P<0.05〕;MR-Egger回归、WM、简单模型及加权模型分析结果显示,甲状腺功能亢进症与HF风险增加无关(P>0.05),但其β值均与IVW的β值方向一致。IVW分析结果显示,甲状腺功能减退症与HF风险增加相关〔OR=1.850,95%CI(1.059~3.233),P<0.05〕;MR-Egger回归、WM、简单模型、加权模型分析结果显示,甲状腺功能减退症与HF风险增加无关(P>0.05),但其β值均与IVW的β值方向一致。Cochran's Q检验结果显示,与甲状腺功能亢进症强相关的SNP间无统计学异质性(P>0.05),与甲状腺功能减退症强相关的SNP间有统计学异质性(P<0.05)。MR-Egger回归的截距项分析结果显示,与甲状腺功能亢进症、甲状腺功能减退症强相关的SNP无水平多效性(P>0.05)。留一法分析结果显示,逐一剔除与甲状腺功能亢进症、甲状腺功能减退症强相关的SNP后,MR分析结果无明显变化。结论甲状腺功能亢进症和甲状腺功能减退症均可增加HF发生风险。Objective To explore the causal relationship between thyroid dysfunction and heart failure(HF)by two-sample Mendelian randomization(MR)analysis.Methods Two-sample MR analysis method was used to obtain the hyperthyroidism data set,hypothyroidism data set and HF data set through IEU OpenGWAS prodect,all of which were derived from the European population.The sample size of the hyperthyroidism data set was 460499,and the number of single nucleotide polymorphisms(SNP)was 24189279;the sample size of the hypothyroidism data set was 473703,and the number of SNP was 11973400;the sample size of HF data set was 486160,and the number of SNP was 24178220.The inverse variance weighting(IVW)was used as the main MR analysis method,and MR-Egger regression,weighted median(WM),simple model,and weighted model were used as secondary MR analysis methods.Cochran'sQtest was used to analyze the statistical heterogeneity among SNP.The intercept term of MR-Egger regression was used to analyze the level pleiotropy of SNP.The effect of single SNP on MR analysis results was analyzed by leave-one-out method.Results The results of IVW analysis showed that hyperthyroidism was associated with an increased risk of HF[OR=1.055,95%CI(1.016-1.095),P<0.05].The results of MR-Egger regression,WM,simple model and weighted model analysis showed that hyperthyroidism was not associated with the increased risk of HF(P>0.05),but theβvalues of hyperthyroidism were consistent with theβvalues of IVW.The results of IVW analysis showed that hypothyroidism was associated with an increased risk of HF[OR=1.850,95%CI(1.059-3.233),P<0.05].The results of MR-Egger regression,WM,simple model and weighted model analysis showed that hypothyroidism was not associated with the increased risk of HF(P>0.05),but theβvalues were consistent with theβvalues of IVW.CochranQtest results showed that there was no statistical heterogeneity between SNP strongly associated with hyperthyroidism(P>0.05),and there was statistical heterogeneity between SNP strongly associated with hypothy

关 键 词：心力衰竭 甲状腺功能亢进症 甲状腺功能减退症 孟德尔随机化分析 因果关系 

分 类 号：R541.62[医药卫生—心血管疾病]