白细胞介素-9水平变化与哮喘关联的双向孟德尔随机化研究

Bidirectional Mendelian randomization study on association between interleukin-9 level change and asthma

目的探讨哮喘与白细胞介素-9(IL-9)水平变化的关联,为早期预防哮喘发生、改善哮喘病情提供参考。方法通过与哮喘、IL-9相关的2项全基因组关联研究(GWAS)收集单核苷酸多态性(SNP)资料。筛选出与IL-9相关的43个SNP为工具变量、哮喘为研究结局进行正向孟德尔随机化(MR)分析,与哮喘相关的3个SNP作为工具变量、IL-9水平变化为研究结局进行反向MR分析。采用Cochran’s Q检验异质性,MR-Egger回归法检验多效性,留一法检验结果的稳健性。结果Cochran’s Q检验显示不存在异质性(P=0.383、0.883),均采用固定效应模型的MR分析。IL-9水平升高导致发生哮喘的风险上升17%(OR=1.17,95%CI:1.02~1.34),发生哮喘导致IL-9水平升高0.09个标准差(OR=1.09,95%CI:1.01~1.19)。逐个剔除SNP后,MR分析结果稳健。MR-Egger回归法未发现工具变量的多效性(P=0.995、0.129)。结论IL-9水平变化与发生哮喘风险之间存在双向基因关联。

Objective To investigate the association between asthma and IL-9 level,to provide reference for early prevention of asthma occurrence and improvement of asthma condition.Methods The data of single nucleotide polymorphism(SNP)were collected from two genome-wide association studies(GWAS)related to asthma and IL-9.Forty-three SNP instrumental variables associated with IL-9 were screened to conduct the forward direction Mendelian randomization(MR)analysis with asthma as the outcome.The three SNP associated with asthma served as the instrumental variables,the IL-9 level change served as the study outcome to conduct the reverse MR analysis.Heterogeneity was detected by using Cochran’s Q test,and the pleiotropy was detected by using the MR-Egger regression method.The robustness of the results was tested by the a leave-one-out method.Results The Q-test showed that no heterogeneity existed(P=0.383,0.883),and the MR analysis of fixed-effects model was used.The IL-9 level increase led to that the asthma occurrence risk was increased by 17%(OR=1.17,95%CI:1.02-1.34).The asthma occurrence led to the IL-9 level increase by 0.09 standard deviation(OR=1.09,95%CI:1.01-1.19).After removing SNP one by one,the MR analysis results were steady.The MR-Egger regression method did not find the pleiotropy of instrumental variables(P=0.995,0.129).Conclusion There are bidirectional gene association between the IL-9 level change and asthma occurrence risk.