Revealing genetic causality between blood-based biomarkers and major depression in east Asian ancestry.

INTRODUCTION

Major Depression (MD) is a common mental disorder. In East Asian ancestry, the association, causality, and shared genetic basis between blood-based biomarkers and MD remain unclear.

METHODS

We investigated the relationships between blood-based biomarkers and MD through a cross-sectional study and Mendelian randomization (MR) analysis. Cross-trait analysis and enrichment analyses were used to highlight the shared genetic determinants and biological pathways. We conducted summary data-based MR to identify shared genes, which were then validated using a transcriptome dataset from drug-naïve patients with MD.

RESULTS

In the cross-sectional study, C-Reactive Protein showed the significantly positive correlation with depressive symptoms, while hematocrit, hemoglobin, and uric acid exhibited significantly negative correlations. In MR analysis, basophil count (BASO) and low-density lipoprotein cholesterol (LDLc) had a significant causal effect on MD. The enrichment analysis indicated a significant role of inflammatory cytokines and oxidative stress. The shared genes , , , and were validated, with identified as a pleiotropic gene involved in MD, BASO, and LDLc.

DISCUSSION

This study highlighted that BASO and LDLc have a causal effect on MD in East Asian ancestry. The pathological mechanisms of MD are related not only to inflammatory cytokines and oxidative stress but also to down regulation of expression and mitochondrial dysfunction.