Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases  

双样本孟德尔随机化分析湿疹与自身免疫性疾病之间的因果关系

作　　者：CHEN Chunli YAN Siyu WAN Bangbei YU Yangyiyi ZENG Jinrong TAN Lina LU Jianyun 陈春里;闫思聿;万邦贝;于杨依依;曾金容;谭丽娜;鲁建云(中南大学湘雅三医院皮肤科,长沙410013;海南省妇幼保健中心生殖医学中心,海口570208)

机构地区：[1]Department of Dermatology,Third Xiangya Hospital,Central South University,Changsha 410013 [2]Reproductive Medical Center,Hainan Women and Children’s Medical Center,Haikou 570208,China

出　　处：《中南大学学报（医学版）》2024年第6期932-942,共11页Journal of Central South University ：Medical Science

基　　金：This work was supported by the National Natural Science Foundation (82273506,82273508);the Hunan Provincial Health Commission Scientific Research Plan Project (D202304128334),China。

摘　　要：Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.目的:湿疹与自身免疫性疾病之间的因果关系尚未见报道。本研究旨在评估湿疹与自身免疫性疾病之间的因果关系。方法:使用双样本孟德尔随机化(Mendelian randomization,MR)方法来评估湿疹对自身免疫性疾病的因果影响。基因组关联研究(Genome-Wide Association Study Catalog,GWAS)汇总数据来自综合流行病学部门(Integrative Epidemiology Unit,IEU)数据库。根据显著性(P<5×10-8)确定湿疹和自身免疫性疾病的遗传工具变异(genetic instrument variants,GIVs)。使用逆方差加权(inverse-variance weighted,IVW)方法生成因果效应估计;MR Egger、最大似然、MR-PRESSO和MR-RAPS方法进行替代分析;异质性、水平多效性和留一分析进行敏感性测试。最后评估反向因果关系。结果:患克罗恩病(Crohn’s disease,CD)(OR=1.444,95%CI 1.199~1.738,P<0.001)和溃疡性结肠炎(ulcerative colitis,UC)(OR=1.002,95%CI 1.001~1.003,P=0.002)的风险随着湿疹的遗传易感性而增加。但其他6种自身免疫性疾病,包括系统性红斑狼疮(systemic lupus erythematosus,SLE)(OR=0.932,P=0.401)、大疱性类天疱疮(bullouspemphigoid, BP)(OR=1.191, P=0.642)、白癜风(OR=1.000, P=0.327)、多发性硬化症(multiple sclerosis,MS)(OR=1.000,P=0.965)、强直性脊柱炎(ankylosing spondylitis,AS)(OR=1.001,P=0.121)和类风湿性关节炎(rheumatoid arthritis,RA)(OR=1.000,P=0.460)与湿疹未见因果关系。同时,自身免疫性疾病与湿疹之间不存在反向因果关系。结论:湿疹患者患CD和UC的风险更高,而湿疹与SLE、MS、AS、RA、BP和白癜风之间无因果关系。

关 键 词：ECZEMA atopic eczema autoimmune diseases Crohn’s disease ulcerative colitis Mendelian randomization 

分 类 号：R758.23[医药卫生—皮肤病学与性病学] R593.2[医药卫生—临床医学]