title: Clinically proven drug targets differentially expressed in the prefrontal cortex of schizophrenia patients.
abstract: BACKGROUND
  Due to the heterogeneous nature of schizophrenia, understanding the genetic risk for the disease is a complex task. Gene expression studies have proven to be more reliable than association studies as they are consistently replicated in a tissue specific manner.
  
  
  METHODS
  Using RNA-Seq we analysed gene expression in the frontal cortex of 24 individuals with schizophrenia and 25 unaffected controls.
  
  
  RESULTS
  We identified 1146 genes that were differentially expressed in schizophrenia, approximately 60% of which were up-regulated and 366 of 1146 (32%) also have aberrant DNA methylation (p=2.46×10-39). The differentially expressed genes were significantly overrepresented in several pathways including inflammatory (p=8.7×10-3) and nitric oxide pathways (p=9.2×10-4). Moreover, these genes were significantly enriched for those with a druggable genome (p=0.04). We identified a number of genes that are significantly up-regulated in schizophrenia as confirmed in other gene expression studies using different brain tissues. Of the 349 genes associated with schizophrenia from the Psychiatric Genomics Consortium we identified 16 genes that are significant from our list of differentially expressed genes.
  
  
  CONCLUSIONS
  Our results identified biological functional genes that are differentially expressed in schizophrenia. A subset of these genes are clinically proven drug targets. We also found a strong pattern of differentially expressed immune response genes that may reflect an underlying defect in schizophrenia.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. Electronic address: j.voisey@qut.edu.au.
authors.forename: Joanne
authors.initials: J
authors.lastname: Voisey
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Divya
authors.initials: D
authors.lastname: Mehta
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: McLeay
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Morris
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Leesa F
authors.initials: LF
authors.lastname: Wockner
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.
authors.forename: Ernest P
authors.initials: EP
authors.lastname: Noble
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Lawford
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Ross McD
authors.initials: RM
authors.lastname: Young
mesh_terms: D019175:DNA Methylation; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D017397:Prefrontal Cortex / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation
keywords: Brain; Gene expression; Immune response; Methylation; RNA-Seq; Schizophrenia