Family-based association study of the NOTCH4 gene in schizophrenia using Japanese and Chinese samples.
BACKGROUND
A family based association study in a British sample found the NOTCH4 gene to be associated with schizophrenia; however, all six replication studies failed to confirm the finding.


METHODS
We performed a family based association study of NOTCH4 and schizophrenia in 123 trios (16 Japanese and 107 Chinese). In addition to the original study's polymorphisms, we examined four new single nucleotide polymorphisms (SNPs)--SNPs_A, B, C and D--around SNP1 of the original study. We genotyped all samples for SNPs_A-D and for SNP1 and (CTG)n of the original study.


RESULTS
We found no significant associations between NOTCH4 and schizophrenia or its subtypes for all polymorphisms, regardless of gender. The finding remained negative when the Chinese sample was analyzed separately. Exploratory analyses suggested that SNP_A may be associated with early-onset schizophrenia and that SNP1 may be associated with schizophrenia characterized by numerous negative symptoms.


CONCLUSIONS
NOTCH4 is not a significant susceptibility gene for schizophrenia when clinical heterogeneity is ignored; however, NOTCH4 may be associated with early-onset schizophrenia or schizophrenia with many negative symptoms, but these findings should be interpreted cautiously.
Takahashi
Sakae
S
Department of Psychiatry, Massachusetts Mental Health Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cui
Yu-hu
YH
Kojima
Takuya
T
Han
Yong-hua
YH
Yu
Shun-ying
SY
Tanabe
Eiici
E
Yara
Kazuo
K
Matsuura
Masato
M
Matsushima
Eisuyke
E
Nakayama
Junko
J
Arinami
Tadao
T
Shen
Yu-cun
YC
Faraone
Stephen V
SV
Tsuang
Ming T
MT
D000328:Adult; D017668:Age of Onset; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002681:China; D005190:Family; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012559:Schizophrenia / Q000235:genetics*
C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch