Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach
Open accessAbstract
Using successful genome-wide association results in psychiatry for drug repurposing is an ongoing challenge. Databases collecting drug targets and gene annotations are growing and can be harnessed to shed a new light on psychiatric disorders. We used genome-wide association study (GWAS) summary statistics from the Psychiatric Genetics Consortium (PGC) Schizophrenia working group to build a drug repositioning model for schizophrenia. As sample size increases, schizophrenia GWAS results show increasing enrichment for known antipsychotic drugs, selective calcium channel blockers, and antiepileptics. Each of these therapeutical classes targets different gene subnetworks. We identify 123 Bonferroni-significant druggable genes outside the MHC, and 128 FDR-significant biological pathways related to neurons, synapses, genic intolerance, membrane transport, epilepsy, and mental disorders. These results suggest that, in schizophrenia, current well-powered GWAS results can reliably detect known schizophrenia drugs and thus may hold considerable potential for the identification of new therapeutic leads. Moreover, antiepileptics and calcium channel blockers may provide repurposing opportunities. This study also reveals significant pathways in schizophrenia that were not identified previously, and provides a workflow for pathway analysis and drug repurposing using GWAS results.
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In the multi-ancestry gene-set analysis of targets of drug classes defined by ATC classes, there was significant enrichment in the targets of four drug classes: Antipsychotics and Psychoanaleptics, which includes individually significant Antidepressants and its subclass Other Antidepressants.
“In the multi-ancestry gene-set analysis of the targets of drug classes defined by their ATC classes (45), there was significant enrichment in the targets of four drug classes: Antipsychotics and Psychoanaleptics, which includes individually significant Antidepressants and its subclass Other Antidepressants”
From GWAS meta-analysis of suicide attempt: identification of 12 genome-wide significant loci and implication of genetic risks for specific health factors (2023) · cites this paper as [45]
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- Authors
- Gaspar, H. A., & Breen, G.
- Affiliations
- National Health Service (GB)
- Corresponding author
- Gaspar, H. A.
- Venue
- Scientific Reports
- Published
- 2017-09-29
- Volume
- 7
- Issue
- 1
- Pages
- 12460-12460
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5622077
- OpenAlex
- W2759241620
- Cited by
- 67
- References
- 8
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 7 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 11 · 2018: 10 · 2017: 1
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Funders
- South London and Maudsley NHS Foundation Trust
- National Institute for Health and Care Research
- King's College London
- University of North Carolina at Chapel Hill
- NIHR Maudsley Biomedical Research Centre
- National Institute of Mental Health (HHSN-271-2013-00017-C, U01MH109528, MH109528)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- schizophrenia, drug repurposing, genome-wide association study, antipsychotic drugs, calcium channel blockers, antiepileptic drugs, druggable genes, biological pathways, pathway analysis, major histocompatibility complex, therapeutic target
- MeSH terms
- Anticonvulsants, Biological Transport, Calcium Channel Blockers, Humans, Nerve Tissue Proteins, Neurons, Pharmacogenetics, Schizophrenia, Synapses, Antipsychotic Agents, Sample Size, Protein Interaction Mapping, Gene Regulatory Networks, Metabolic Networks and Pathways, Genome-Wide Association Study, Drug Repositioning, Molecular Targeted Therapy
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