Assessing the causal relationship between immune cell traits and depression by Mendelian randomization analysis

Background: Observational studies suggested that immune system disorder is associated with depression. However, the causal association has not been fully elucidated. Thus, we aim to assess the causality of the associations of immune cell profiles with risk of depression through Mendelian randomization analysis.

Methods: We extracted genetic variances of immune cell traits from a large publicly available genome-wide association study (GWAS) involving 3757 participants and depression from a GWAS containing 246,363 cases and 561,190 controls of European ancestry. Inverse variance weighting (IVW) was performed as the MR primary analysis. Simultaneously apply MR-Egger and weighted median as supplementary enhancements to the final result. We further performed heterogeneity and horizontal pleiotropy test to validate the main MR results.

Results: Five immunophenotypes were identified to be significantly associated with depression risk: CD27 on IgD^-CD38^dimB cell (OR = 1.019, 95 % CI = 1.010-1.028, P = 1.24 × 10^-5), CD45RA^-CD4⁺T cell Absolute Count (OR = 0.974, 95 % CI = 0.962-0.986, P = 3.88 × 10^-5), CD40 on CD14^-CD16⁺monocyte (OR = 0.987, 95 % CI = 0.981-0.993, P = 2.1 × 10^-4), CD27 on switched memory B cell (OR = 1.015, 95 % CI = 1.006-1.023, P = 2.6 × 10^-4), CD27 on IgD^-CD38^-B cell (OR = 1.017, 95 % CI = 1.008-1.027, P = 3.1 × 10^-4).

Conclusion: Our findings shed light on the intricate interaction pattern between the immune system and depression, offering a novel direction for researchers to investigate the underlying biological mechanisms of depression.