Comparative genomic evidence for the involvement of schizophrenia risk genes in antipsychotic effects

Genome-wide association studies (GWAS) for schizophrenia have identified over 100 loci encoding >500 genes. It is unclear whether any of these genes, other than dopamine receptor D , are immediately relevant to antipsychotic effects or represent novel antipsychotic targets. We applied an in vivo...

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Published inMolecular psychiatry Vol. 23; no. 3; pp. 708 - 712
Main Authors Kim, Y, Giusti-Rodriguez, P, Crowley, J J, Bryois, J, Nonneman, R J, Ryan, A K, Quackenbush, C R, Iglesias-Ussel, M D, Lee, P H, Sun, W, de Villena, F P-M, Sullivan, P F
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.03.2018
Subjects
Animals
Antipsychotic Agents - therapeutic use
Antipsychotics
Brain - drug effects
Brain - metabolism
Care and treatment
Corpus Striatum - drug effects
Corpus Striatum - metabolism
Development and progression
Dopamine D2 receptors
Gene Expression Regulation - drug effects
Genes
Genetic aspects
Genetic diversity
Genetic Predisposition to Disease - genetics
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genomics - methods
Genotypes
Haloperidol
Haloperidol - metabolism
Haloperidol - pharmacology
Health aspects
Male
Medicin och hälsovetenskap
Mental disorders
Methods
Mice
Mice, Inbred C57BL
Psychotropic drugs
Ribonucleic acid
Risk Factors
RNA
Schizophrenia
Schizophrenia - genetics
Schizophrenic Psychology
Sequence Analysis, RNA
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Summary:Genome-wide association studies (GWAS) for schizophrenia have identified over 100 loci encoding >500 genes. It is unclear whether any of these genes, other than dopamine receptor D , are immediately relevant to antipsychotic effects or represent novel antipsychotic targets. We applied an in vivo molecular approach to this question by performing RNA sequencing of brain tissue from mice chronically treated with the antipsychotic haloperidol or vehicle. We observed significant enrichments of haloperidol-regulated genes in schizophrenia GWAS loci and in schizophrenia-associated biological pathways. Our findings provide empirical support for overlap between genetic variation underlying the pathophysiology of schizophrenia and the molecular effects of a prototypical antipsychotic.
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These authors contributed equally
ISSN:1359-4184
1476-5578
1476-5578
DOI:10.1038/mp.2017.111