Mendelian Randomization Study of Immune Cells and Pediatric Asthma

DU Sijie; ZHENG Liwei; QU Xiujun; HE Li; WANG Xiao; LI Shumin; ZANG Caihong

doi:10.13730/j.issn.2097-2148.2025.06.005

Abstract：Objective To investigate the causal relationship between immune cells and pediatric asthma by two-sample Mendelian randomization(MR).Methods Data on immune cells and pediatric asthma were extracted from public-ly available data of genome-wide association studies(GWAS),causal inferences were then performed using the inverse va-riance weighted(IVW),MR Egger regression,weighted median estimator(WME)and weighted mode(WM),a series of sensitivity analysis were conducted to validate the robustness of the results.Results A total of 10 types of immune cells were detected,with statistically significant differences(P＜0.05).Among these,3 immune cell subsets Basophil％CD33dim HLA DR-CD66b-,CD33 on Granulocytic Myeloid-Derived Suppressor Cells and CX3CR1 on CD14-CD16-were identified as potentially promoting the development of pediatric asthma,conversely,the remaining seven immune cell subsets,including CD39+resting CD4 regulatory T cell Absolute Count,CD3 on activated CD4 regulatory T cell,CD3 on activated & secreting CD4 regulatory T cell,CD28 on CD28+CD45RA+CD8+T cell,HLA DR on myeloid Dendritic Cell,HLA DR on plasmacytoid Dendritic Cell and HLA DR on Dendritic Cell,were associated with the decreased risk of pediatric asthma.All 10 immune cell subsets passed the tests for heterogeneity,sensitivity and pleiotropy analysis.MR analysis and sensitivity analysis showed that,Basophil％CD33dim HLA DR-CD66b-,CD33 on Granulocytic Myeloid-Derived Suppressor Cells and CX3CR1 on CD14-CD16-were risk factors for childhood asthma,and the other 7 were protective factors for childhood asthma;reverse MR analyzing IVM showed that,pediatric asthma was not a sufficient condition for the changes in these 10 immune cells.Conclusion Ten kinds of immune cells have been confirmed to have a causal relationship with the pathogen-esis of childhood asthma by genetic means.