Identifying potential pathogenic oxidative stress-related genes in depression through multi-omics summary-data-based...

Area of Science:

• Genetics and Molecular Biology
• Neuroscience
• Psychiatry

Background:

• The precise relationship between oxidative stress-related genes (OSGs) and the development of depression is not fully understood.
• Investigating these genetic links is crucial for understanding depression pathophysiology.

Purpose of the Study:

• To investigate potential causal associations between OSGs and depression susceptibility.
• To identify specific OSGs that may play a role in depression risk.

Main Methods:

• A Summary-data-based Mendelian randomization (SMR) approach was utilized.
• Depression-related OSGs (DeOSGs) were identified by intersecting differentially expressed genes in depression with known OSGs.
• SMR analyses integrated methylation (mQTL), expression (eQTL), and protein (pQTL) quantitative trait loci data.

Main Results:

• 488 DeOSGs were identified in depression patients.
• Significant associations were found between 130 methylation sites, 28 genes, and three proteins and depression risk.
• Four genes—BRAF, CUTA, SLC27A3, and SMARCA4—were identified as potential key players, influencing depression via methylation and expression.

Conclusions:

• BRAF, CUTA, SLC27A3, and SMARCA4 are implicated in depression risk through epigenetic and gene expression modifications.
• These identified genes represent potential novel targets for therapeutic interventions and biomarker development in depression research.