Purpose:The etiology of schizophrenia is extensively debated, and multiple factors have been contended to be involved. A panoramic view of the contributing factors in a genomewide study can be an effective strategy to provide a comprehensive understanding of its causality.
Materials and Methods: GSE53987 dataset downloaded from GEO-database, which comprised mRNA expression data of post-mortem brain tissue across three regions from control and age-matched subjects of schizophrenia (N= Hippocampus (HIP): C-15, T-18, Prefrontal cortex (PFC): C-15, T-19, Associative striatum (STR): C-18, T-18). Bio-conductor 'affy' package used to compute mRNA expression, and further t-test applied to investigate differential gene expression. The functional and disease association analyses of the derived genes performed using PANTHER Classification System, GeneCards and NCBI database.Results: A set of 40 genes showed significantly altered (p<0.01) expression across all three brain regions (38 protein coding, 2 noncoding). The functional analysis revealed, genes involved in maintaining basic housekeeping functions as catalysis (44.7%), binding (34.2%), and nucleic acid binding transcription factor activity (13.2%), transporter activity (10.50%), enzyme regulation (7.90%), and structural molecule activity (5.3%), and implicated in biological processes and events, and molecular pathways relating basic neuronal functions.The gene set found associated with neoplasm, inflammatory/immune cell, and immunodeficiency/virus-mediated, neurodegenerative and neurological, metabolic, and congenital diseases respectively.
Conclusions:The functional analysis of the gene set unravels gross components of the multifactorial etiology of schizophrenia. The deviant expression of genes maintaining basic cell machinery explains compromised neuronal processing, and associated pathology may involve intricate mechanisms shared with various other diseases.