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A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
Family-based association study of the NOTCH4 gene in schizophrenia using Japanese and Chinese samples
Sakae Takahashi1, Yu-hu Cui, Takuya Kojima
1Department of Psychiatry, Massachusetts Mental Health Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
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.
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