Causal relationship between immune cells and obesity risk:Univariate bidirectional and multivariate Mendelian randomization study

Objective This study aims to explore the causal relationship between immune cells and obesity risk using the Mendelian randomization (MR) method. Methods Data sets for 731 types of immune cells and obesity were obtained from the Genome Wide Association Study (GWAS) catalog database. The inverse-variance weighted method, weighted median, and other methods were used to investigate the causal relationship between immune cells and obesity.The stability of the results was evaluated using Cochran's Q test,MR-Egger regression,and the leave-one-out method.Results A potential causal relationship(P<0.05)was identified between 32 types of immune cells and obesity.Among them, the causal relationship between classical dendritic cells (cDC, CD80 on CD62L+myeloid DC,P<0.001)and obesity was the most stable(P<0.001),showing a negative causal relationship with obesity risk (OR=0.956, 95% CI: 0.931-0.982).Additionally, reverse MR analysis revealed a positive causal relationship between obesity and TBNK cells(CD45 on lymphocytes,P=0.043,OR=1.372,95%CI:1.010-1.865),indicating a mutual positive causal relationship between CD45 on lymphocytes and obesity risk. Sensitivity analyses confirmed the stability of both forward and reverse results. Multivariate MR analysis showed that when all 32 immune cell traits were simultaneously activated, only TBNK cells (CD16-CD56 on NK cells, P=0.016,OR=1.107, 95% CI:1.019-1.203) had a positive causal relationship with obesity. Conclusion This study preliminarily reveals the causal relationship between immune cells and obesity from a genetic perspective, providing an important theoretical basis for future precision medicine and individualized treatment.