Genetically determined causality between immune cells and anxiety disorders: A Mendelian randomization study

Prior investigations have endeavored to unveil the connection between immune cells and anxiety disorders. However, the majority are limited to a single or few indicators and have not comprehensively evaluated the causal relationship between immune cells and anxiety disorders. In this study, we performed a two-sample Mendelian randomization (MR) analysis to assess the relationship between 731 immune phenotypes and anxiety disorders, offering genetic evidence to substantiate the correlation between immune phenotypes and the risk of anxiety disorders. Using publicly available data from genome-wide association studies on immune phenotypes and anxiety disorders, we selected instrumental variables that met specified criteria. Employing inverse-variance weighting and MR-Egger regression analysis methods, we assessed the causality between 731 immune cell factors and the risk of anxiety disorders. MR-Egger intercept tests, Cochran Q tests, and leave-one-out sensitivity analyses were performed to ascertain the pleiotropy, heterogeneity, and stability of the genetic variations. The primary MR method (inverse-variance weighting) analysis revealed a significant causal correlation between 32 immune phenotypes and anxiety disorders. Following multivariable MR adjustments, 5 exposure factors demonstrated a significant association with anxiety disorders: CD80 on myeloid dendritic cell (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1.00-1.10, P = .010), CD39+ CD8+ T cell %T cell (OR = 0.98, 95% CI = 0.97-1.00, P = .032), CD39+ CD8+ T cell absolute count (OR = 0.98, 95% CI = 0.97-1.00, P = .025), human leukocyte antigen-DR isotype on monocyte (OR = 0.97, 95% CI = 0.94-0.99, P = .013), CD4 on naive CD4+ T cell4 (OR = 0.95, 95% CI = 0.91-1.00, P = .048). Reverse MR suggested an impact of anxiety disorders on 21 immune phenotypes. Our study established an association between immune phenotypes and anxiety disorders, offering a novel avenue for exploring and gaining deeper insights into the pathogenic mechanisms of anxiety disorders. Additionally, these findings provide an immunological perspective that could be valuable for the clinical diagnosis and intervention of anxiety disorders.