title: RNA-Seq analysis implicates dysregulation of the immune system in schizophrenia.
abstract: BACKGROUND
  While genome-wide association studies identified some promising candidates for schizophrenia, the majority of risk genes remained unknown. We were interested in testing whether integration gene expression and other functional information could facilitate the identification of susceptibility genes and related biological pathways.
  
  
  RESULTS
  We conducted high throughput sequencing analyses to evaluate mRNA expression in blood samples isolated from 3 schizophrenia patients and 3 healthy controls. We also conducted pooled sequencing of 10 schizophrenic patients and matched controls. Differentially expressed genes were identified by t-test. In the individually sequenced dataset, we identified 198 genes differentially expressed between cases and controls, of them 19 had been verified by the pooled sequencing dataset and 21 reached nominal significance in gene-based association analyses of a genome wide association dataset. Pathway analysis of these differentially expressed genes revealed that they were highly enriched in the immune related pathways. Two genes, S100A8 and TYROBP, had consistent changes in expression in both individual and pooled sequencing datasets and were nominally significant in gene-based association analysis.
  
  
  CONCLUSIONS
  Integration of gene expression and pathway analyses with genome-wide association may be an efficient approach to identify risk genes for schizophrenia.
authors.affiliation: Department of psychiatry, School of Medicine, University at Buffalo, SUNY, Buffalo, NY 14260, USA.
authors.forename: Junzhe
authors.initials: J
authors.lastname: Xu
authors.forename: Jingchun
authors.initials: J
authors.lastname: Sun
authors.forename: Jingchun
authors.initials: J
authors.lastname: Chen
authors.forename: Lily
authors.initials: L
authors.lastname: Wang
authors.forename: Anna
authors.initials: A
authors.lastname: Li
authors.forename: Matthew
authors.initials: M
authors.lastname: Helm
authors.forename: Steven L
authors.initials: SL
authors.lastname: Dubovsky
authors.forename: Silviu-Alin
authors.initials: SA
authors.lastname: Bacanu
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.forename: Xiangning
authors.initials: X
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism; D055106:Genome-Wide Association Study; D006801:Humans; D007107:Immune System / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D017423:Sequence Analysis, RNA
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D040501:Calgranulin A; D008565:Membrane Proteins; D012333:RNA, Messenger; C110546:TYROBP protein, human