Mendelian randomization study on body mass index and 25 types of autoimmune diseases
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NETL
NSTL
万方数据
维普
目的 采用孟德尔随机化(MR)研究方法探讨体质指数(BMI)与25种自身免疫性疾病(AD)的因果关系.方法 BMI和25种AD的全基因组关联研究(GWAS)数据均来自IEU OPEN GWAS数据库;以与BMI相关的单核苷酸多态性(SNP)为工具变量,以25种AD为研究结局,采用逆方差加权法(IVW)进行MR分析.采用Cochran Q检验评估异质性,采用MR-Egger回归法和MR-PRESSO检验水平多效性,采用留一法评估结果的稳健性.结果 Cochran Q检验存在异质性(P<0.05),采用随机效应模型.MR分析结果显示,BMI升高会增加1型糖尿病(OR=1.519,95%CI:1.281～1.801)、IgA肾病(OR=1.227,95%CI:1.134～1.327)、成人斯蒂尔病(OR=1.002,95%CI:1.001～1.003)、多发性硬化(OR=1.303,95%CI:1.115～1.523)、发作性睡病(OR=1.029,95%CI:1.017～1.040)、桥本甲状腺炎(OR= 1.561,95%CI:1.391～1.751)、自身免疫性肝炎(OR=1.481,95%CI:1.076～2.038)、类风湿关节炎(OR=1.209,95%CI:1.054～1.386)、寻常型银屑病(OR=1.719,95%CI:1.427～2.070)和恶性贫血(OR=1.001,95%CI:1.000～1.002)的发病风险.未发现与其他AD存在统计学关联(均P>0.05).MR-Egger回归法未检测到水平多效性(均P>0.05);MR-PRESSO检测到部分存在水平多效性(均P<0.05),校正结果与原结果一致(P>0.05).留一法显示结果稳健.结论 BMI与1型糖尿病、IgA肾病、成人斯蒂尔病、多发性硬化、发作性睡病、桥本甲状腺炎、自身免疫性肝炎、类风湿关节炎、寻常型银屑病和恶性贫血可能存在因果关系.
Objective To examine the causal relationship between body mass index(BMI)and 25 types of autoimmune diseases(ADs)using Mendelian randomization(MR)study method.Methods The genome-wide association study(GWAS)data for BMI and 25 types of ADs were obtained from IEU OPEN GWAS database.Single nucleotide polymor-phisms(SNPs)related to BMI were used as instrumental variables,25 types of ADs were used as study outcomes,and MR analysis was performed using inverse variance weighted(IVW)method.Heterogeneity was evaluated using Cochran's Q test,horizontal pleiotropy was tested using MR-Egger regression and MR-PRESSO,and results robustness was veri-fied with leave-one-out method.Results Cochran's Q test showed heterogeneity of MR analysis results(P<0.05),and a random effect model was employed.The results of MR analysis showed that elevated BMI increased the incidence risks of type 1 diabetes mellitus(OR=1.519,95%CI:1.281-1.801),IgA nephropathy(OR=1.227,95%CI:1.134-1.327),adult Still disease(OR=1.002,95%CI:1.001-1.003),multiple sclerosis(OR=1.303,95%CI:1.115-1.523),narcolepsy(OR= 1.029,95%CI:1.017-1.040),Hashimoto thyroiditis(OR=1.561,95%CI:1.391-1.751),autoimmune hepatitis(OR=1.481,95%CI:1.076-2.038),rheumatoid arthritis(OR=1.209,95%CI:1.054-1.386),psoriasis vulgaris(OR=1.719,95%CI:1.427-2.070)and pernicious anemia(OR=1.001,95%CI:1.000-1.002).No causal relationship was found with other ADs(all P>0.05).MR-Egger regression identified no horizontal pleiotropy of instrumental variables(all P>0.05),while MR-PRESSO test identified partial horizontal pleiotropy(all P<0.05),which remained consistent with the original results af-ter adjustment(P>0.05).Leave-one-out analysis showed results robustness.Conclusion There are causal relationship among BMI and type 1 diabetes mellitus,IgA nephropathy,adult Still disease,multiple sclerosis,narcolepsy,Hashimoto thyroiditis,autoimmune hepatitis,rheumatoid arthritis,psoriasis vulgaris and pernicious anemia.
Mendelian randomizationbody mass indexautoimmune disease
NETL
NSTL
万方数据
维普
