Integrative Analysis Reveals Human Endogenous Retroviruses-Linked Immune Signatures in Schizophrenia Publisher



M Karimzadeh MOHAMMAD ; F Zakizadeh FARANAK ; F Bokharaeisalim FARAH ; V Omranifard VICTORIA ; S Kiani SOROOR ; Mh Razizadeh Mohammad HOSSEIN
Source: Journal of NeuroVirology Published:2025

Abstract

Schizophrenia is a complex psychiatric disorder with multifactorial etiologies, including genetic components. The role of Human endogenous retroviruses has been suggested in schizophrenia pathogenesis. This study aims to identify and analyze the shared genetic components between schizophrenia and Human endogenous retroviruses through bioinformatics approaches. Genes associated with schizophrenia and Human endogenous retroviruses were identified and analyzed for overlap. A protein-protein interaction network was constructed, followed by hub gene selection using various algorithms. Functional enrichment analyses were conducted to determine biological processes and pathways involved. Transcription factors and miRNA networks were built to investigate gene regulation. Drug and chemical interactions were examined, and gene-disease associations were assessed. Also, gene expression levels in different brain regions and brain and blood cells were analyzed. Logistic regression analysis was done to evaluate the association of hub genes with schizophrenia. A total of 345 genes were found common between schizophrenia and Human endogenous retroviruses. Six hub genes (AKT1, CD4, CD8A, IL6, STAT1, and TNF) were identified. Gene ontology and pathway analyses indicated immune system involvement. Gene expression analysis showed differential expression patterns in blood and brain cells. IL6 and TNF were significantly upregulated in schizophrenia patients, while AKT1 exhibited downregulation. Logistic regression revealed IL6 and TNF as risk factors, whereas AKT1 showed protective effects. This study found key genetic interactions between schizophrenia and endogenous human retroviruses, with hub genes playing significant roles in immune signaling and neuroinflammation. These findings introduce potential targets for therapeutic interventions in schizophrenia. © 2025 Elsevier B.V., All rights reserved.