摘要
目的运用孟德尔随机化(MR)研究方法,探索免疫细胞与过敏性鼻炎的因果联系。方法通过全基因组关联研究(GWAS)数据库获取731种免疫细胞和过敏性鼻炎的GWAS数据,采用两样本双向MR分析方法,以逆方差加权法(IVW)作为主要分析方法,以加权中位数法、MR-Egger回归法、简单模式法和加权模式法作为辅助分析方法,进行异质性检验、多效性检验和留一法等敏感性分析,对初步结果进行Bonferroni校正以增加结果的可靠性与严谨性。结果两样本正向MR分析结果显示,67种免疫细胞表型与过敏性鼻炎存在相关性。经Bonferroni校正,最终筛选出4种免疫细胞表型,其中CD3在CD39阳性活化CD4调节性T细胞上的表达(OR=0.953,95%CI:0.931~0.978,P<0.001,P_(adj)=0.007)、疱疹病毒入侵介导因子(HVEM)在CD45RA阴性CD4^(+)T细胞上的表达(OR=0.965,95%CI:0.948~0.983,P<0.001,P_(adj)=0.008)和人类白细胞抗原-DR(HLA-DR)高表达的单核细胞占白细胞的百分比(OR=0.929,95%CI:0.885~0.974,P=0.002,P_(adj)=0.157)是过敏性鼻炎的保护因素;过渡性B细胞占B细胞的百分比(OR=1.094,95%CI:1.032~1.161,P=0.003,P_(adj)=0.183)是过敏性鼻炎的危险因素。反向MR分析未发现过敏性鼻炎与4种免疫细胞表型存在因果关系。结论两样本正向MR分析证实免疫细胞与过敏性鼻炎存在因果联系,且MR分析具有减少混杂因素干扰和避免反向因果等优点,为深入研究过敏性鼻炎的免疫机制、敏感生物标志物及药物治疗靶点提供了理论依据。
Objective To explore the causal association between immune cells and allergic rhinitis using Mendelian randomization(MR)approach.Methods GWAS data for 731 types of immune cells and allergic rhinitis were obtained from genome-wide association study(GWAS)databases.A two-sample bidirectional MR analysis was conducted,with the inverse-variance weighted(IVW)method as the primary analytical approach,and the weighted median method,MR-Egger regression,simple mode method,and weighted mode method as supplementary approaches.Sensitivity analyses,including heterogeneity tests,pleiotropy tests,and the leave-one-out method,were performed.Bonferroni correction was applied to the preliminary results to enhance their reliability and rigor.Results The two-sample forward MR analysis revealed correlations between 67 immune cell phenotypes and allergic rhinitis.After Bonferroni correction,four immune cell phenotypes were finally identified.Among them,the expression of CD3 on CD39-positive activated CD4 regulatory T cells(OR=0.953,95%CI,0.931 to 0.978,P<0.001,P_(adj)=0.007),the expression of herpesvirus entry mediator(HVEM)on CD45RA-negative CD4^(+)T cells(OR=0.965,95%CI,0.948 to 0.983,P<0.001,P_(adj)=0.008),and the percentage of human leukocyte antigen class DR(HLA-DR)-high-expressing monocytes among leukocytes(OR=0.929,95%CI,0.885 to 0.974,P=0.002,P_(adj)=0.157)were protective factors for allergic rhinitis.In contrast,the percentage of transitional B cells among B cells(OR=1.094,95%CI,1.032 to 1.161,P=0.003,P_(adj)=0.183)was a risk factor for allergic rhinitis.The reverse MR analysis showed no causal relationship between allergic rhinitis and the four immune cell phenotypes.Conclusion The two-sample forward MR analysis confirms a causal link between immune cells and allergic rhinitis.MR analysis has the advantages of reducing confounding factor interference and avoiding reverse causation,providing a theoretical basis for in-depth research on immune mechanisms,sensitive biomarkers,and drug treatment targets of allergic rhinitis.
作者
位式祥
于会勇
李磊
刘莲莲
聂天旸
谢楚溪
解子乐
柯殷泽
陈天韵
王成祥
WEI Shixiang;YU Huiyong;LI Lei;LIU Lianlian;NIE Tianyang;XIE Chuxi;XIE Zile;KE Yinze;CHEN Tianyun;WANG Chengxiang(Department of Respiratory Medicine,the Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing,100029;Infectious Department,the Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing,100029)
出处
《实用临床医药杂志》
2025年第14期39-44,共6页
Journal of Clinical Medicine in Practice
基金
国家自然科学基金资助项目(82074389)
首都卫生发展科研专项基金资助项目(首发2022-2-7034)。
关键词
孟德尔随机化
免疫细胞
过敏性鼻炎
因果关系
全基因组关联研究
敏感生物标志物
保护因素
危险因素
Mendelian randomization
immune cells
allergic rhinitis
causal relationship
genome-wide association study
sensitive biomarkers
protective factors
risk factors
