GEO2R Analysis of Depression-Related Co-expression Differential Genes Reveals Close Associations with Multiple Nutrients

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Objective: To elucidate the pathophysiological mechanisms of depression at the genetic level and its correlation with various nutrients by analyzing raw data from open databases. Methods: Studies supporting GEO2R analysis of human depression-related gene analyses in the GEO database were retrieved. Co-DEGs were screened for functional and pathway enrichment, PPI, and HUB gene analyses. Results: 3,039 studies on human depression-related gene analysis in the GEO database were identified. After screening, 5 sets of gene core DEGs (Padj < 0.05 & |FC| > 1.2) were obtained, and Venn analysis yielded 2 sets of Co-DEGs (108 up-regulated, 112 downregulated). Functional enrichment showed that Co-DEGs are involved in protein synthesis, signal transduction, RNA regulation, enzymatic reaction regulation, and ATP metabolism; pathway enrichment was found in cell membrane function, inflammatory response, with multiple pathways involving calcium ion homeostasis imbalance, GSK3β, Wnt/β-catenin. PPI analysis identified 10 proteins with high centrality (node degree ≥ 3): TGFA, ITGA1, ITGA2, ITGA2B, RTCA, TRMT13, CCND1, GPSM3, KLRG1, and NSUN6; Cytoscape software analysis identified 10 HUB genes: ITGA2B, ITGA5, ITGA1, ITGA2, TRMT13, NSUN6, TRMT10C, KLRG1, RTCA, and CCR1. The integrin family among these proteins and genes has complex and close connections with nutrients, including amino acids, vitamins, and trace minerals, especially tryptophan associated with the platelet subunit encoded by ITGA2B; non-integrin genes TRMT10C, TRMT13, and NSUN6 encode SAM-dependent methyltransferases, and the G-protein function encoded by GPSM3 is modified by n-3. Conclusion: The pathophysiological mechanisms at the genetic level of depression suggest that the onset, progression, and intervention of the disease are closely related to various nutrients. Targeted research and clinical strategies may contribute to progress in the fields of depression and nutrition.

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