title: Association analysis of FEZ1 variants with schizophrenia in Japanese cohorts.
abstract: BACKGROUND
  DISC1 has been suggested as a causative gene for psychoses in a large Scottish family. We recently identified FEZ1 as an interacting partner for DISC1. To investigate the role of FEZ1 in schizophrenia and bipolar disorder, case-control association analyses were conducted in Japanese cohorts.
  
  
  METHODS
  We performed a mutation screen of the FEZ1 gene and detected 15 polymorphisms. Additional data on informative polymorphisms were obtained from public databases. Eight single nucleotide polymorphisms (SNPs) were analyzed in 119 bipolar disorder and 360 schizophrenic patients and age- and gender-matched control subjects. All genotypes were determined with the TaqMan assay, and selected samples were confirmed by sequencing.
  
  
  RESULTS
  The two adjacent polymorphisms displayed a nominally significant association with schizophrenia (IVS2+ 1587G>A, p = .014; 396T<A or Asp123Glu, p = .024). Homozygotes with the Glu123 allele were observed in only a small portion (2%) of schizophrenia patients but not in control subjects or bipolar patients. Conversely, no SNPs displayed allelic, genotypic, or haplotypic associations with bipolar disorder.
  
  
  CONCLUSIONS
  A modest association between FEZ1 and schizophrenia suggests that this gene and the DISC1-mediated molecular pathway might play roles in the development of schizophrenia, with FEZ1 affecting only a small subset of Japanese schizophrenia patients.
authors.affiliation: RIKEN Brain Science Institute, Laboratory for Molecular Psychiatry, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Minabe
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama-Shigeno
authors.forename: Hitomi
authors.initials: H
authors.lastname: Takao
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Eiji
authors.initials: E
authors.lastname: Hattori
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Takei
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.forename: Ko
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Akiko
authors.initials: A
authors.lastname: Honda
authors.forename: Kousuke
authors.initials: K
authors.lastname: Baba
authors.forename: Taiichi
authors.initials: T
authors.lastname: Katayama
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D012559:Schizophrenia / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C528597:FEZ1 protein, human; C118711:LZTS1 protein, human; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins