双样本孟德尔随机化分析血嗜酸性粒细胞与变应性鼻炎的因果关系

Two-sample Mendelian randomization analysis of the causal relationship between blood eosinophils and allergic rhinitis

目的:既往研究揭示了嗜酸性粒细胞与变应性鼻炎之间的相关性,但其因果关系尚未得到充分证实。本研究采用孟德尔随机化(Mendelian randomization,MR)方法对血嗜酸性粒细胞与变应性鼻炎之间的因果联系进行评估。方法:先汇总嗜酸性粒细胞计数(暴露变量)和变应性鼻炎(结局变量)的基因组关联研究(Genome-Wide Association Study Catalog,GWAS)数据,其中暴露变量的GWAS数据来源于布里斯托大学的综合流行病学部门(Integrative Epidemiology Unit,IEU)所开发的IEU Open GWAS Project,结局变量的GWAS数据则来源于芬兰基因生物银行(FinnGen Biobank)数据库;再采用逆方差加权(inverse variance weighted,IVW)的双样本MR方法分析嗜酸性粒细胞与变应性鼻炎的因果关系,并通过加权中位数法、MR-Egger回归法、留一法(leave-one-out)和漏斗图来进行敏感性分析。结果:血嗜酸性粒细胞计数的增加与变应性鼻炎风险的增加存在潜在因果关系(OR=1.187,95%CI 1.051~1.341,P=0.006)。加权中位数法和MR-Egger回归法也得到相同的结果。留一法结果显示没有单个单核苷酸多态性对因果推断产生显著影响。结论:嗜酸性粒细胞计数的增加与变应性鼻炎风险的增加或病情的加重有因果关联。

Objective:Previous studies have revealed a correlation between eosinophils and allergic rhinitis,but the causal relationship has not been fully confirmed.This study aims to evaluate the causal link between blood eosinophils and allergic rhinitis using the Mendelian randomization(MR)method.Methods:Summary data from the Genome-Wide Association Study Catalog(GWAS)for eosinophil count(exposure variable)and allergic rhinitis(outcome variable)were collected.GWAS data for the exposure variable were obtained from the IEU Open GWAS Project developed by the Integrative Epidemiology Unit at the University of Bristol,while data for the outcome variable were sourced from the FinnGen Biobank(Finland)database.The causal relationship between eosinophils and allergic rhinitis was analyzed using the two-sample MR method with inverse variance weighted(IVW)analysis.Sensitivity analyses were conducted using the weighted median method,MR-Egger regression,leave-one-out analysis,and funnel plots.Results:An increase in blood eosinophil count showed a potential causal relationship with an increased risk of allergic rhinitis(OR=1.187,95%CI 1.051 to 1.341,P=0.006).This finding was consistent across the weighted median method and MR-Egger regression.Leave-one-out analysis indicated that no single nucleotide polymorphism significantly influenced the causal inference.Conclusion:There is a causal association between increased eosinophil count and a higher risk or worsening of allergic rhinitis.