目的 采用两样本孟德尔随机化(Mendelian randomization,MR)方法研究多种白细胞介素(interleukin,IL)水平与患肺结核风险的因果关联.方法 IL和肺结核的数据分别来自3项公开发表的欧洲人群全基因组关联研究(genome-wide association studies,GWAS)汇总数据.根据预设的阈值和连锁不平衡等要求从汇总数据中提取了与多种IL密切相关的单核苷酸多态性(single nucleotide polymorphism,SNP)位点作为工具变量,研究主要采用逆方差加权(inverse vari-ance weighted,IVW)、MR-Egger 回归和加权中位数估计法(weighted median estimator,WME)评估 9种IL水平与肺结核风险之间的因果效应.同时,对结果进行了水平多效性和异质性的检验以保证其稳定性,采用方向性检验检查是否存在反向因果效应.结果 IVW结果显示,尚未发现IL-1RA、IL-2RA、IL-6、IL-6RA、IL-8、IL-17、IL-I8 与肺结核风险之间存在因果关联(均 P>0.05)o IL-16水平的增加与肺结核风险增加有关(OR=1.210,95%CI:1.032~1.419,P=0.019,P校正=0.086),而IL-27水平的增加与肺结核风险降低有关(OR=0.875,95%CI:0.788~0.970,P=0.011,P校正=0.086),结果在3种MR方法中稳定并且方向一致,同时不存在反向因果关系.结论 尚未发现IL-1RA、IL-2RA、IL-6、IL-6RA、IL-8、IL-17、IL-I8与肺结核之间存在因果关联.IL-16水平的增加与肺结核风险增加有关,而IL-27水平的增加与肺结核风险降低有关.
Mendelian randomization study on the causal relationship between interleukins and pulmonary tuberculosis
Objective This study aims to determine the causal association between multiple interleukin(IL)levels and the risk of tuberculosis by using a two-sample Mendelian randomization(MR)method.Methods The data on interleukins and tuberculosis were obtained from the the pooled data of three published genome-wide association studies(GWAS)accomplished in European populations.According to preset thresholds and requirements of linkage disequilibrium,the single nucleotide polymorphism(SNP)loci closely related to a variety of interleukins were extracted from the summarized data as instrumental variables,the causal effect of nine interleukin levels on the risk of tuberculosis was assessed by using inverse variance weighting(IVW),mr-egger regression,and weighted median estima-tion.At the same time,the horizontal pleiotropy and heterogeneity were tested to ensure the stability of the results,and the directional test was used to check reverse causality effect.Results According to the IVW results,there were no causal relationships among interleukins of IL-1RA,IL-2RA,IL-6,IL-6RA,IL-8,IL-17,IL-18 and pulmonary tuberculosis(P>0.05).Higher levels of 1L-16 were correlated with an increased risk of tuberculosis(OR=1.210,95%CI:1.032-1.419,P=0.019,Padjusted=0.086).In contrast,rised IL-27 levels suggested a lower risk of tuberculosis(OR=0.875,95%CI:0.788-0.97,P=0.011,Padjusted=0.086).These findings remained robust and consistent across all three MR testing methods with no reverse causality.Conclusions No causal relationship has been found among interleu-kins of IL-1RA,IL-2RA,IL-6,IL-6RA,IL-8,IL-17,IL-18 and pulmonary tuberculosis.Higher IL-16 levels are linked to an increased risk of developing tuberculosis,while the increase in IL-27 levels is associated with a decreased risk of pulmonary tuberculosis.
Mendelian randomizationInterleukinsPulmonary tuberculosisCausal association