体质指数与25种自身免疫性疾病的孟德尔随机化研究

Mendelian randomization study on body mass index and 25 types of autoimmune diseases

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 MRPRESSO 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.