摘要
目的:基于孟德尔随机化(MR)方法,探讨41种细胞因子与特应性皮炎(AD)的双向因果关联。方法:利用41种细胞因子和AD的全基因组关联研究(GWAS)汇总数据进行工具变量(IV)的筛选,并通过MR-PRESSO的离群值检验以及MR Steiger filtering方法排除影响MR分析结果的单核苷酸多态性(SNP)。使用逆方差加权(IVW)法、MR-Egger回归和加权中值法(WM)进行两样本双向MR分析。MR-Egger截距项检验和Cochran's Q检验对IV的多效性和异质性进行检验,并通过散点图、漏斗图和留一图对MR结果进行可视化。结果:正向MR分析结果显示,MIG(IVW:OR=0.89;95%CI:0.81~0.97;P=0.006)会降低AD发病的风险。而IL-5(IVW:OR=1.17;95%CI:1.01~1.36;P=0.042)和IL-18(MR Egger:OR=1.17;95%CI:1.03~1.33;P=0.030)则会增加AD发病风险。反向MR分析结果显示,AD与MIG(IVW:Beta=0.10;95%CI:0.02~0.17;P=0.014)的增加有潜在的因果关联。敏感性分析均未表明纳入的IV具有多效性与异质性。结论:MIG可能是AD进展过程中的重要标志物,与发病风险之间具有潜在的双向因果关联。IL-5与IL-18对AD具有潜在的正向因果关联。
Objective:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MREgger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81~0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01~1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03~1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02~0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.
作者
李伟佳
彭怡
黄巧
王朴
胡敏
潘素跃
刘凌宇
戚嘉慧
江千帆
何玉清
LI Weijia;PENG Yi;HUANG Qiao;WANG Pu;HU Min;PAN Suyue;LIU Lingyu;QI Jiahui;JIANG Qian-fan;HE Yuqing(Department of Epidemiology and Health Statistics,School of Public Health,Institute of Medi-cal Systems Biology,Guangdong Medical University,Dongguan 523808,China;Dongguan Liaobu Hospital,Dongguan 523400,China)
出处
《中国免疫学杂志》
北大核心
2025年第8期1914-1919,共6页
Chinese Journal of Immunology
基金
国家自然科学基金(81773312)
广东省“扬帆计划引进紧缺拔尖”人才项目(201433005)。
关键词
特应性皮炎
细胞因子
孟德尔随机化
因果推断
Atopic dermatitis
Cytokines
Mendelian randomization
Causal inference
