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免疫细胞与过敏性鼻炎的因果关系: 一项两样本双向孟德尔随机化研究

Causal relationship between immune cells and allergic rhinitis: a two-sample bidirectional mendelian randomization

    摘要
  • 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, Padj=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, Padj=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, Padj=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, Padj=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。

     

    Abstract:
    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, Padj=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, Padj=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, Padj=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, Padj=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.

     

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