title: ANXA7, PPP3CB, DNAJC9, and ZMYND17 genes at chromosome 10q22 associated with the subgroup of schizophrenia with deficits in attention and executive function.
abstract: BACKGROUND
  A genome scan of Taiwanese schizophrenia families suggested linkage to chromosome 10q22.3. We aimed to find the candidate genes in this region.
  
  
  METHODS
  A total of 476 schizophrenia families were included. Hierarchical clustering method was used for clustering families to homogeneous subgroups according to their performances of sustained attention and executive function. Association analysis was performed using family-based association testing and TRANSMIT. Candidate associated regions were identified using the longest significance run method. The relative messenger RNA expression level was determined using real-time reverse transcriptase polymerase chain reaction.
  
  
  RESULTS
  First, we genotyped 18 microsatellite markers between D10S1432 and D10S1239. The maximum nonparametric linkage score was 2.79 on D10S195. Through family clustering, we found the maximum nonparametric linkage score was 3.70 on D10S195 in the family cluster with deficits in attention and executive function. Second, we genotyped 79 single nucleotide polymorphisms between D10S1432 and D10S580 in 90 attention deficit and execution deficit families. Association analysis indicated significant transmission distortion for nine single nucleotide polymorphisms. Using the longest significance run method, we identified a 427-kilobase region as a significant candidate region, which encompasses nine genes. Third, we studied messenger RNA expression of these nine genes in Epstein-Barr virus-transformed lymphoblastic cells. In schizophrenic patients, there was significantly lower expression of ANXA7, PPP3CB, and DNAJC9 and significantly higher expression of ZMYND17.
  
  
  CONCLUSIONS
  ANXA7, PPP3CB, DNAJC9, and ZMYND17 genes are potential candidate genes for schizophrenia, especially in patients with deficits in sustained attention and executive function. The responsible functional variants remained to be clarified.
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital, Yun Lin Branch, Yunlin, Taiwan.
authors.forename: Chih-Min
authors.initials: CM
authors.lastname: Liu
authors.forename: Cathy S-J
authors.initials: CS
authors.lastname: Fann
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Liu
authors.forename: Yen-Jen
authors.initials: YJ
authors.lastname: Oyang
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Yang
authors.forename: Chien-Ching
authors.initials: CC
authors.lastname: Chang
authors.forename: Chun-Chiang
authors.initials: CC
authors.lastname: Wen
authors.forename: Wei J
authors.initials: WJ
authors.lastname: Chen
authors.forename: Tzung-Jeng
authors.initials: TJ
authors.lastname: Hwang
authors.forename: Ming H
authors.initials: MH
authors.lastname: Hsieh
authors.forename: Chen-Chung
authors.initials: CC
authors.lastname: Liu
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.forename: Hai-Gwo
authors.initials: HG
authors.lastname: Hwu
mesh_terms: D000328:Adult; D017310:Annexin A7 / Q000096:biosynthesis / Q000235:genetics*; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics*; D019703:Calcineurin / Q000096:biosynthesis / Q000235:genetics*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D056344:Executive Function / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies / Q000379:methods; D008040:Genetic Linkage; D005838:Genotype; D050956:HSP40 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D012565:Schizophrenic Psychology
chemical_list: D017310:Annexin A7; D002352:Carrier Proteins; C494654:DNAJC9 protein, human; D050956:HSP40 Heat-Shock Proteins; D019703:Calcineurin; C525674:PPP3CB protein, human