循环炎性细胞因子和支气管哮喘的风险:孟德尔随机化分析

Circulating inflammatory cytokines and the risk of bronchial asthma:A Mendelian randomization analysis

目的利用孟德尔随机化探究循环炎性细胞因子与支气管哮喘(哮喘)之间的因果关系。方法一项8 293名健康参与者的公开全基因组关联研究(GWAS)摘要的循环炎性细胞因子作为暴露数据, 一项大型GWAS(56 167例病例和352 255名欧洲血统对照)的哮喘遗传变异作为结局数据, 通过两样本孟德尔随机化方法评估41个循环炎性细胞因子与哮喘的因果关系, 并利用多种方法进行敏感性检验。结果干扰素γ水平(OR=1.017, 95%CI:1.005~1.029, P=0.005)和肿瘤坏死因子α水平(OR=1.047, 95%CI:1.004~1.092, P=0.031)与哮喘风险增加有关, 白细胞介素1受体拮抗剂(OR=0.952, 95%CI:0.909~0.997, P=0.031)是哮喘发病的保护因素, 其他炎性细胞因子与哮喘之间没有因果关系。结论干扰素γ和肿瘤坏死因子α是哮喘发病的危险因素, 可能促进哮喘发生;白细胞介素1受体拮抗剂和哮喘发病具有负相关因果关系, 是哮喘的保护因素。

of 8293 healthy participants were used as exposure data and asthma genetic variants from a large GWAS(56167 cases and 352255 controls of European ancestry)were used as outcome data.A two-sample Mendelian randomization approach was used to assess the causal relationship between 41 circulating inflammatory cytokines and asthma,and sensitivity tests were performed using multiple methods.Results The results showed that interferon gamma level(OR=1.017,95%CI:1.005-1.029,P=0.005)and tumor necrosis factor alpha level(OR=1.047,95%CI:1.004-1.092,P=0.031)were associated with increased risk of asthma,and interleukin-1 receptor antagonist(OR=0.952,95%CI:0.909-0.997,P=0.031)was a protective factor for asthma development,and there was no causal relationship between other inflammatory cytokines and asthma.Conclusions This study suggests that interferon gamma and tumor necrosis factor alpha are risk factors for the development of asthma and may contribute to asthma;interleukin-1 receptor antagonist has a negative causal relationship with asthma development,thus the protective factor of asthma.