Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach

Abstract 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) sum...

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Autores principales:	H. A. Gaspar, G. Breen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4fb5cf2ef0a5453dba3fd3a890202636
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spelling	oai:doaj.org-article:4fb5cf2ef0a5453dba3fd3a8902026362021-12-02T11:52:19ZDrug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach10.1038/s41598-017-12325-32045-2322https://doaj.org/article/4fb5cf2ef0a5453dba3fd3a8902026362017-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-12325-3https://doaj.org/toc/2045-2322Abstract 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.H. A. GasparG. BreenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q H. A. Gaspar G. Breen Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach
description	Abstract 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.
format	article
author	H. A. Gaspar G. Breen
author_facet	H. A. Gaspar G. Breen
author_sort	H. A. Gaspar
title	Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach
title_short	Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach
title_full	Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach
title_fullStr	Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach
title_full_unstemmed	Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach
title_sort	drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4fb5cf2ef0a5453dba3fd3a890202636
work_keys_str_mv	AT hagaspar drugenrichmentanddiscoveryfromschizophreniagenomewideassociationresultsananalysisandvisualisationapproach AT gbreen drugenrichmentanddiscoveryfromschizophreniagenomewideassociationresultsananalysisandvisualisationapproach
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Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach

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