Association analysis of FEZ1 variants with schizophrenia in Japanese cohorts.
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.
Yamada
Kazuo
K
RIKEN Brain Science Institute, Laboratory for Molecular Psychiatry, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Nakamura
Kazuhiko
K
Minabe
Yoshio
Y
Iwayama-Shigeno
Yoshimi
Y
Takao
Hitomi
H
Toyota
Tomoko
T
Hattori
Eiji
E
Takei
Noriyoshi
N
Sekine
Yoshimoto
Y
Suzuki
Katsuaki
K
Iwata
Yasuhide
Y
Miyoshi
Ko
K
Honda
Akiko
A
Baba
Kousuke
K
Katayama
Taiichi
T
Tohyama
Masaya
M
Mori
Norio
N
Yoshikawa
Takeo
T
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*
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