Exploring the bi-directional relationship and shared genes between depression and stroke via NHANES and bioinformatic...

Area of Science:

• Genomics and Bioinformatics
• Neuroscience
• Immunology

Background:

• Stroke and major depressive disorder (MDD) are leading global causes of disability.
• A bidirectional relationship exists between stroke and MDD, but underlying molecular mechanisms remain unclear.
• Understanding shared pathways is crucial for developing effective treatments for these interconnected conditions.

Purpose of the Study:

• To identify shared hub genes and biological pathways in ischemic stroke (IS) and MDD.
• To analyze immune cell infiltration in patients with IS and MDD.
• To explore potential therapeutic targets for the comorbidity of IS and MDD.

Main Methods:

• Analysis of the NHANES dataset (2005-2018) to assess the association between stroke and MDD.
• Identification of common differentially expressed genes (DEGs) between IS and MDD datasets (GSE98793, GSE16561).
• Functional enrichment, pathway analysis, and regulatory network construction using bioinformatics tools (GO, KEGG, Metascape, GeneMANIA, NetworkAnalyst, DGIdb); ssGSEA for immune infiltration analysis.

Main Results:

• Stroke significantly associated with MDD (OR=2.79, p<0.0001) in 29,706 participants.
• Identified 41 common upregulated and 8 common downregulated genes between IS and MDD, primarily involved in immune responses.
• Discovered ten hub genes (e.g., CD163, AEG1, HP) and constructed regulatory networks, revealing activated innate immunity and suppressed acquired immunity in both disorders.

Conclusions:

• Ten shared hub genes and their regulatory networks link ischemic stroke and major depressive disorder.
• These findings provide novel molecular insights into the comorbidity of IS and MDD.
• The identified hub genes represent potential therapeutic targets for managing comorbid stroke and depression.