Chellappa, SA and Pathak, AK and Sinha, P and Jainarayanan, AK and Jain, S and Brahmachari, SK (2019) Meta-analysis of genomic variants and gene expression data in schizophrenia suggests the potential need for adjunctive therapeutic interventions for neuropsychiatric disorders. In: Journal of Genetics, 98 (2).
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Abstract
Schizophrenia (SZ) is a debilitating mental illness with a multigenic aetiology and significant heritability. Despite extensive genetic studies, the molecular aetiology has remained enigmatic. A recent systems biology study suggested a protein–protein interaction network for SZ with 504 novel interactions. The onset of psychiatric disorders is predominant during adolescence, often accompanied by subtle structural abnormalities in multiple regions of the brain. The availability of BrainSpan Atlas data allowed us to re-examine the genes present in the SZ interactome as a function of space and time. The availability of genomes of healthy centenarians and nonpsychiatric Exome Aggregation Consortium database allowed us to identify the variants of criticality. The expression of the SZ candidate genes responsible for cognition and disease onset was studied in different brain regions during particular developmental stages. A subset of novel interactors detected in the network was further validated using gene expression data of post-mortem brains of patients with psychiatric illness. We have narrowed down the list of drug targets proposed by the previous interactome study to 10 proteins. These proteins belonging to 81 biological pathways are targeted by 34 known Food and Drug Administration-approved drugs that have distinct potential for the treatment of neuropsychiatric disorders. We also report the possibility of targeting key genes belonging to celecoxib pharmacodynamics, G α signalling and cGMP-PKG signalling pathways that are not known to be specific to SZ aetiology.
| Item Type: | Journal Article |
|---|---|
| Publication: | Journal of Genetics |
| Publisher: | Springer |
| Additional Information: | The copyright for this article belongs to Springer. |
| Keywords: | biological marker; neuroleptic agent; transcriptome, adolescent; adult; data mining; drug effect; gene expression profiling; gene expression regulation; genetic database; genetic predisposition; genetic variation; genetics; genome-wide association study; human; mental disease; meta analysis; molecularly targeted therapy; schizophrenia; workflow; young adult, Adolescent; Adult; Antipsychotic Agents; Biomarkers; Data Mining; Databases, Genetic; Gene Expression Profiling; Gene Expression Regulation; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Mental Disorders; Molecular Targeted Therapy; Schizophrenia; Transcriptome; Workflow; Young Adult |
| Department/Centre: | Division of Interdisciplinary Sciences > Supercomputer Education & Research Centre |
| Date Deposited: | 27 Dec 2022 04:29 |
| Last Modified: | 27 Dec 2022 04:29 |
| URI: | https://eprints.iisc.ac.in/id/eprint/78548 |
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