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
Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases
陈春里 1闫思聿 1万邦贝 2于杨依依 1曾金容 1谭丽娜 1鲁建云1
作者信息
- 1. 中南大学湘雅三医院皮肤科,长沙 410013
- 2. 海南省妇幼保健中心生殖医学中心,海口 570208
- 折叠
摘要
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)、大庖性类天疱疮(bullous pemphigoid,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.
Abstract
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.
关键词
湿疹/特应性湿疹/自身免疫性疾病/克罗恩病/溃疡性结肠炎/孟德尔随机化Key words
eczema/atopic eczema/autoimmune diseases/Crohn's disease/ulcerative colitis/Mendelian randomization引用本文复制引用
基金项目
National Natural Science Foundation(82273506)
National Natural Science Foundation(82273508)
Hunan Provincial Health Commission Scientific Research Plan Project,China(D202304128334)
出版年
2024
NETL
NSTL
万方数据