Mendelian Randomization Analysis of the Causal Association Between IL-6 Mediated Childhood Obesity and Childhood Asthma

ZENG Qingjia; WANG Mengqing; SUN Guixiang; HU Yan; SHUAI Yunfei; XUN Chunzheng; DENG Chengguo; LI Fan

doi:10.13730/j.issn.2097-2148.2025.01.004

Abstract：Objective To explore the causal relationship between childhood obesity,interleukin 6(IL-6)and child-hood asthma by mendelian randomization(MR)analysis.Methods Based on the published data set of genome-wide asso-ciation studies in European population,the relationship among childhood obesity,IL-6 and childhood asthma was analyzed by 5 MR analysis methods,including inverse variance weighted(IVM),MR-Egger,Weighted median,Simple mode and Weighted mode,which IVW test was considered as the main method.Horizontal pleiotropy was detected by MR-Egger regression and MR pleiotropy residual sum and outlier(MR-PRESSO),and heterogeneity was detected by Cochran's Q test,the sensitivity analysis was analyzed by leave-one-out method.After MR analysis,the mediated effect value and the proportion of the intermediate effect were calculated.Finally,the reverse MR study was used to explore the relationship among childhood obesity,IL-6 and childhood asthma.Results In two-sample MR analysis,IVW tests showed that childhood obesity(OR=1.039,P=0.023)and IL-6(OR=1.139,P=0.034)were causally related to childhood asthma,the childhood obesity was causally related to IL-6(OR=1.056,P=0.010).The mediated effect value of IL-6 in the causal relationship between childhood obesity and childhood asthma was 0.004 and the direct effect was 0.035.The MR-Egger regression and MR-PRESSO tests showed that both the intercept and the global P value were greater than 0.05,the single nucleotide polymorphism(SNP)selected was not polymorphism,and the causal infer-ence method was effective.MR analysis of childhood obesity-IL-6 and childhood obesity-childhood asthma and MR analy-sis of IL-6-childhood asthma showed heterogeneity(P＜0.01),and the others were not(P＞0.05).In reverse MR analy-sis,I VW test showed that there was no the reverse causal relationship among childhood asthma and childhood obesity,childhood asthma and IL-6,IL-6 and childhood obesity(P＞0.05).Conclusion Both childhood obesity and IL-6 have a causal and positive correlation with childhood asthma,and IL-6 is an incomplete mediator in the causal relationship be-tween childhood obesity and childhood asthma.