Abstract
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 genome-wide 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 multi-factorial 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.