title: Targeting the schizophrenia genome: a fast track strategy from GWAS to clinic.
abstract: The Psychiatric Genomics Consortium-Schizophrenia Workgroup (PGC-SCZ) has recently published a genomewide association study (GWAS) identifying >100 genetic loci, encompassing a total of 341 protein-coding genes, attaining genomewide significance for susceptibility to schizophrenia. Given the extremely long time (12-15 years) and expense (>$1 billion) associated with the development of novel drug targets, repurposing of drugs with known and validated targets may be the most expeditious path toward deriving clinical utility from these GWAS findings. In the present study, we examined all genes within loci implicated by the PGC-SCZ GWAS against databases of targets of both approved and registered pharmaceutical compounds. We identified 20 potential schizophrenia susceptibility genes that encode proteins that are the targets of approved drugs. Of these, we prioritized genes/targets that are of clear neuropsychiatric interest and that are also sole members of the linkage disequilibrium block surrounding a PGC-SCZ GWAS hit. In addition to DRD2, 5 genes meet these criteria: CACNA1C, CACNB2, CACNA1I, GRIN2A and HCN1. An additional 20 genes coding for proteins that are the targets of drugs in registered clinical trials, but without approved indications, were also identified. Although considerable work is still required to fully explicate the biological implications of the PGC-SCZ GWAS results, pathways related to these known, druggable targets may represent a promising starting point.
authors: 1] Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA [2] Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA [3] Departments of Psychiatry and Molecular Medicine, Hofstra University School of Medicine, Hempstead, NY, USA.
authors: T
authors: T
authors: Lencz
authors: 1] Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA [2] Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA [3] Departments of Psychiatry and Molecular Medicine, Hofstra University School of Medicine, Hempstead, NY, USA.
authors: A K
authors: AK
authors: Malhotra
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D002986:Clinical Trials as Topic; D030541:Databases, Genetic; D062313:Databases, Pharmaceutical; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents