A Mendelian randomization study: causal relationship between immune cells and the risks of social phobia, specific phobia, and agoraphobia.

Background: Although phobia is a common psychiatric disorder, the underlying biological mechanisms have not been fully elucidated. Complex immune-brain interactions that affect neural development, survival, and function may have causal and therapeutic implications in psychiatric illnesses. In this study, the relationships between immune cell traits and phobia were analysed using Mendelian randomization to explore the biological mechanisms.

Methods: Based on publicly-available genetic data, a two-sample MR analysis was used to determine the causal relationship between 731 immune cell traits and the risk of developing phobias. Sensitivity analyses were conducted to verify the robustness, heterogeneity, and horizontal pleiotropy of the results.

Results: After forward and reverse analyses, false discovery rate (FDR) corrections were performed. No significant associations between phobias and immune cell traits were identified. After adjusting the FDR threshold, social phobia affected two immune cell traits: CD39 on granulocytes (β = 9.0347, 95% confidence interval (CI) = 4.4802-13.5891, P = 0.0001, FDR = 0.0738), and CD11c on granulocytes (β = 7.7976, 95% CI = 3.4616-12.1336, P = 0.0004, FDR = 0.1547). Three immune cell traits affected the risk of specific phobias: CD4 + CD8dim T cell %leukocyte (odds ratio (OR) = 0.9985, 95% CI = 0.9976-0.9993, P = 0.0006, FDR = 0.1373), CD45 on CD33 + HLA DR + CD14dim (OR = 0.9977, 95% CI = 0.9964-0.9990, P = 0.0004, FDR = 0.1373), and CD8 on CD28 + CD45RA + CD8br (OR = 0.9990, 95% CI = 0.9985-0.9996, P = 0.0003, FDR = 0.1373). Two immune cell traits affected the risk of agoraphobia: CD3 on CD39 + resting regulatory T cells (Tregs) (OR = 1.0010, 95 CI%=1.0005-1.0015, P = 0.0001, FDR = 0.0596) and HLA DR on CD33br HLA DR + CD14dim (OR = 0.9993, 95 CI%=0.9990-0.9997, P = 0.0002, FDR = 0.0596).

Conclusions: Immune cell traits closely related to phobias were screened out through genomics, which provides a reference for the subsequent research on the immune system-phobia interaction.