儿童期肥胖与2型糖尿病、冠心病的孟德尔随机化研究  

Association among childhood obesity,type 2 diabetes mellitus and coronary artery heart disease:a Mendelian randomization study

作　　者：陈海苗 马岩[1] 刘明奇 马珊珊[1] 李军 方益荣[1] CHEN Haimiao;MA Yan;LIU Mingqi;MA Shanshan;LI Jun;FANG Yirong(Shaoxing Center for Disease Control and Prevention,Shaoxing,Zhejiang 312000,China)

机构地区：[1]绍兴市疾病预防控制中心,浙江绍兴312000

出　　处：《预防医学》2025年第3期307-311,共5页China Preventive Medicine Journal

摘　　要：目的探究儿童期肥胖与2型糖尿病(T2DM)、冠心病(CHD)的因果关联。方法儿童期肥胖的全基因组关联研究(GWAS)数据来自ECG汇总的2~18岁儿童资料(18613名病例和12696名对照),T2DM的GWAS数据来自DIAGRAM汇总的资料(242283名病例和1569734名对照),CHD的GWAS数据来自CARDIoGRAMplusC4D汇总的资料(10801名病例和137371名对照)。采用MAGMA、PLACO和条件错误发现率(cFDR)方法分析与T2DM、CHD均相关的多效性基因;采用逆方差加权法(IVW)进行孟德尔随机化(MR)分析,探究儿童期肥胖、T2DM和CHD的因果关联;采用Cochran Q检验评估异质性;采用MR-Egger回归法检验水平多效性;采用MR-PRESSO检验去除离群值。进一步采用中介分析探究三者中的中介变量。结果MAGMA、PLACO和cFDR分析结果显示,与T2DM、CHD均相关的多效性基因有80个,主要分布于3号、17号和19号染色体。MR分析结果显示,儿童期肥胖增加T2DM(OR=1.151,95%CI:1.033~1.283)、CHD(OR=1.158,95%CI:1.068~1.255)的发病风险;T2DM增加CHD的发病风险(OR=1.182,95%CI:1.139~1.227),CHD也增加T2DM的发病风险(OR=1.124,95%CI:1.055~1.198)。MR-Egger回归法未发现水平多效性,MR-PRESSO检验未发现离群值(均P>0.05)。中介分析结果显示,儿童期肥胖可直接正向影响CHD(效应值=0.096,95%CI:0.012~0.180),也可通过T2DM间接正向影响CHD(效应值=0.023,95%CI:0.005~0.041),中介效应占总效应的15.65%。结论儿童期肥胖与T2DM、CHD存在因果关联,T2DM与CHD互为因果关联;T2DM在儿童期肥胖与CHD间发挥中介作用。Objective To investigate the association between childhood obesity and type 2 diabetes mellitus(T2DM)as well as coronary artery heart disease(CHD).Methods Genome-wide association study(GWAS)data for childhood obesity were collected from the ECG consortium,encompassing information on children aged 2 to 18 years,including 18613 cases and 12696 controls.GWAS data for T2DM were collected from the DIAGRAM consortium,including 242283 cases and 1569734 controls.GWAS data for CHD were collected from the CARDIoGRAMplusC4D consortium,including 10801 cases and 137371 controls.Pleiotropic genes associated with both T2DM and CHD were analyzed using the MAGMA,PLACO and conditional false discovery rate(cFDR)methods.Mendelian randomization(MR)analysis was performed using inverse variance weighted(IVW)method,exploring the causal relationships among childhood obesity,T2DM and CHD.Heterogeneity was evaluated using Cochran's Q test,horizontal pleiotropy and exclude outliers were tested using MR-Egger regression and MR-PRESSO test.The mediating variables among the three diseases were investigated by using a mediation analysis.Results The results of MAGMA,PLACO and cFDR analyses identified 80 pleiotropic genes associated with both T2DM and CHD,primarily distributed on chromosomes 3,17 and 19.The MR analysis revealed that childhood obesity increased the risk of T2DM(OR=1.151,95%CI:1.033-1.283)and CHD(OR=1.158,95%CI:1.068-1.255),T2DM increased the risk of CHD(OR=1.182,95%CI:1.139-1.227),and CHD increased the risk of T2DM(OR=1.124,95%CI:1.055-1.198).The MR-Egger regression analysis showed no horizontal pleiotropy,and the MR-PRESSO test did not identify any outliers(all P>0.05).Mediation analysis indicated that childhood obesity directly increased the risk of CHD(effect value=0.096,95%CI:0.012-0.180)and indirectly increased the risk of CHD through T2DM(effect value=0.023,95%CI:0.005-0.041),with the mediation effect accounting for 15.65%of the total effect.Conclusions There are potential causal associations between childhood obesity and T2

关 键 词：肥胖 2型糖尿病 冠心病 孟德尔随机化 中介分析 

分 类 号：R723.14[医药卫生—儿科]