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

Area of Science:

• Immunology and Psychiatry
• Genetic Epidemiology

Background:

• Previous research explored immune cell links to anxiety disorders but lacked comprehensive causal evaluations.
• Existing studies often focused on limited immune indicators, hindering a full understanding of the immune system's role.

Purpose of the Study:

• To genetically investigate the causal relationship between 731 immune phenotypes and anxiety disorders using a two-sample Mendelian randomization approach.
• To identify specific immune factors that causally influence the risk of developing anxiety disorders.

Main Methods:

• Conducted a two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association study data for immune phenotypes and anxiety disorders.
• Employed inverse-variance weighting and MR-Egger regression, with sensitivity analyses (MR-Egger intercept, Cochran Q, leave-one-out) to ensure robustness and assess pleiotropy and heterogeneity.

Main Results:

• Identified a significant causal correlation between 32 immune phenotypes and anxiety disorders via primary MR analysis.
• After multivariable MR adjustments, five immune factors showed significant associations: CD80 on myeloid dendritic cells, CD39+ CD8+ T cell percentage and count, HLA-DR on monocytes, and CD4 on naive CD4+ T cells.
• Reverse MR indicated anxiety disorders impact 21 immune phenotypes.

Conclusions:

• Established a genetic association between specific immune phenotypes and anxiety disorders, suggesting a role in pathogenesis.
• Findings offer novel insights into anxiety disorder mechanisms and potential immunological targets for clinical diagnosis and intervention.