基于孟德尔随机化探讨炎症因子与儿童哮喘的因果关联

Exploration of the Causal Relationship Between Inflammatory Cytokines and Childhood Asthma Based on Mendelian Randomization

目的:通过孟德尔随机化(MR)方法来探究炎症因子与儿童哮喘之间的因果关系。方法:将从3个芬兰队列(n=8 293)研究中测量到的41种炎性细胞因子的循环水平用作暴露因素,筛选出与暴露因素强相关且相互独立的单核苷酸多态性作为有效工具变量。从GWAS数据库中获取包含3 025名儿童哮喘患者和135 449名对照个体的数据集(finn-b-ASTHMA_CHILD)以用作研究的结局变量。通过“TwoSampleMR”R软件包进行两样本MR分析,以风险值(OR)来评估炎症因子与儿童哮喘之间的因果关联。通过留一法对所得结果进行敏感性分析,利用MR-Egger intercept和MR-PRESSO global test来检验水平多效性,Cochran’s Q检测异质性。结果:IVW方法分析所得结果表明IL-2 (OR=0.835,95%CI:0.717~0.973,P=0.021)与儿童哮喘存在显著负相关。利用留一法进行敏感性分析发现因果关系的结果表现稳定,MR-Egger intercept和MR-PRESSO global test检验无水平多效性,Cochran’s Q检验不存在异质性。结论:炎症因子IL-2和儿童哮喘之间存在因果关系,IL-2可降低儿童哮喘的发病风险。

Objective:To explore the causal relationship between inflammatory cytokines and childhood asthma based on Mendelian randomization(MR).Methods:Circulating levels of 41 inflammatory cytokines measured from 3 Finnish cohort studies(n=8293)were used as exposure factors.Single nucleotide polymorphisms that were strongly correlated with exposure factors and independent of each other were selected as effective instrumental variables.A childhood asthma dataset(finn-b-ASTHMA_CHILD)with 3025 patients and 135449 controls was downloaded from the GWAS database as the outcome variable.Two-sample MR Analysis was performed by“TwoSampleMR”R software package to evaluate the causal association between inflammatory cytokines and childhood asthma with risk value.Sensitivity analysis was performed by leave-one-out method.Horizontal pleiotropy was tested by MR-Egger intercept and MR-PRESSO global test,and Cochran’s Q test was used for heterogeneity.Results:IVW analysis showed that IL-2(OR=0.835,95%CI:0.717~0.973,P=0.021)was negatively correlated with childhood asthma.In addition,the results of leave-one-out sensitivity analysis were stable,MR-Egger intercept and MR-PRESSO global test showed no horizontal pleiotropy,and Cochran’s Q test showed no heterogeneity.Conclusion:There is a causal relationship between IL-2 and childhood asthma.IL-2 can reduce the risk of childhood asthma.