Schizophrenia: Identification of Hub Genes for its Diagnosis

Janhavi Patil, Symbiosis School of Biological Sciences, Pune

What is Schizophrenia?

Many mental disorders are prevalent today. Considered a clinical syndrome, Schizophrenia is commonly diagnosed in people today. Disordered thinking, hallucinations, and inability to concentrate, express emotions and carry out daily chores are some common manifestations of this mental disorder. Disease diagnosis is given on the basis of symptoms, but Schizophrenia shares symptoms with various other mental disorders, making accurate diagnosis challenging. Analyzing specific genes contributing to the disease can help as a diagnostic marker. 

Schizophrenia May Have a Genetic Basis

Even though the exact cause of this disease is unknown, many studies suggest genetics has a role in the development of Schizophrenia. This research, too, considered the genetic basis and tried to study the “hub” genes that might contribute to Schizophrenia by obtaining datasets from existing databases. Hub genes are those which show high co-relation and can contribute to the development of a disease.

Getting Information on the Board

The datasets were obtained from the GEO database maintained by NCBI. The analysis was performed using existing software available on the internet. The data sets were subjected to extraction through analysis of gene expression profiles which gave information about differently expressed genes. A control group of healthy individuals was also maintained. 

Analyzing the Information using Bioinformatics

The DEGs were subjected to GO and KEGG pathway enrichment analysis using DAVID. Gene ontology refers to a framework that is used to study the functions of gene products of a biological system using computational tools. Biological process (BP), cellular component (CC), and molecular function (MF) are 3 significant levels of GO analysis. The KEGG database is widely used to study biological pathways, drugs, chemicals, and genomes. Filtered DEGs were also subjected to protein-protein interaction analysis (using STRING), gene mi-RNA analysis (using NetworkAnalyst), immune infiltration analysis (using CIBERSORTx), and diagnostic values were analyzed using the open characteristic (ROC) curve drawing tool.

Connecting the Dots

After performing all the analyses mentioned before 4 hub genes with diagnostic values were identified-NFKBIA, CDKN1A, BTG2, and GADD45B. All these genes share a common feature of being involved in biological processes related to cell cycle, DNA, and nucleus which are a suggestion of a strong genetic basis behind Schizophrenia.

CDKN1A and GADD45B are highly expressed in schizophrenic patients. The schizophrenic population also shows a significantly higher number of resting CD4-T cells. Gene mi-RNA analysis showed that NFKBIA and BTG 2 genes were significantly correlated with resting CD4-T cells which might be contributing to immune disorder in these patients. Upon further study and verification, these genes might prove as potential biomarkers for diagnosis and therapeutic agents.

Also read: Negative thinking styles in COVID-19 survivors and cognitive vulnerability

Reference:

Feng, S., Sun, P., Qu, C., Wu, X., Yang, L., Yang, T., Wang, S., Fang, Y., & Chen, J. (2022). Exploring the core genes of schizophrenia based on bioinformatics analysis. Genes, 13(6), 967. https://doi.org/10.3390/genes13060967

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