Revealing the Causal Relationship Between Differential White Blood Cell Counts and Depression: A Bidirectional...

Area of Science:

• Immunology
• Psychiatry
• Genetics

Background:

• The relationship between white blood cells (WBC) and depression is complex and not fully understood.
• Previous studies suggest a link, but the direction of causality remains unclear.
• Investigating bidirectional causal relationships is crucial for understanding this interplay.

Purpose of the Study:

• To determine the bidirectional causal links between six specific white blood cell counts and depression.
• To leverage large-scale genome-wide association studies (GWAS) for robust analysis.
• To apply Mendelian randomization (MR) to infer causality.

Main Methods:

• Utilized a two-sample Mendelian randomization (MR) approach.
• Employed summary statistics from large GWAS datasets for depression (N=406,986) and WBC counts (N=563,085).
• Applied various MR methods including IVW, MR-Egger, and weighted median, with FDR correction for significance.

Main Results:

• Reverse MR showed depression causally increases overall WBC count (p=0.044 FDR) and basophil count (p=0.038 FDR).
• A marginally significant causal effect of depression on increasing lymphocyte count was observed (p=0.071 FDR).
• Forward MR suggested monocyte count may decrease depression risk (p=0.028), but this was not significant after FDR correction.

Conclusions:

• Depression appears to causally impact the immune system, increasing WBC and basophil counts.
• Elevated lymphocyte counts are marginally associated with depression.
• Higher monocyte counts may have a protective effect against depression, requiring further investigation.