基于双样本孟德尔随机化研究731种免疫细胞与儿童肥胖的因果关系OA

Objective To investigate the causal relationship between 731 immune cells and childhood obesity using two-sample Mendelian randomization(MR).Methods Single nucleotide polymorphism(SNP)associated with exposure and outcome were selected from the genome-wide association study(GWAS)datasets.SNP significantly associated with exposure data(P<1e-5)and with F>10 were selected as instrumental variable(IV).731 immune cells were selected as exposure factors,childhood obesity as an outcome factor.Five commonly used methods were used to evaluate the causal link,among which the inverse variance weighted(IVW)method was the main evaluation method.Results MR analysis revealed that 18 immune cell phenotypes were significantly associated with the risk of childhood obesity(P<0.05).11 immune cell phenotypes were positively associated with the risk of childhood obesity:IgD-CD38-%B cell,CD62L-myeloid DC%DC cell,CD33br HLA DR+CD14-%CD33br HLA DR+myeloid cell,CD3 on CM CD4+T cell,CD3 on CM CD8br T cell,CD3 on CD39+secreting Treg cell,CD3 on CD45RA+CD4+Treg cell,CD3 on CD8br Treg cell,CD3 on CD28+CD4+Treg cell,CD3 on CD28+CD45RA+CD8br Treg cell,CD86 on myeloid DC cell.7 immune cell phenotypes are negatively associated with the risk of childhood obesity:Activated and resting Treg AC cell,Naive CD8br%T cell,CD8dim NKT AC TBNK cell,CD8dim NKT%lymphocyte TBNK cell,CD25 on CD39+CD4 Treg cell,CD25 on resting Treg cell,CD8 on CD28+CD45RA-CD8br Treg cell.Conclusion Through two-sample MR,this study reveals the complex relationship between various immune cells and childhood obesity,offering diverse immunological perspectives for the diagnosis and treatment of pediatric obesity.