Considerable evidence implicates the disrupted in schizophrenia 1 (DISC1) gene in schizophrenia susceptibility. DISC1 was initially implicated in the aetiology of schizophrenia after a balanced translocation between chromosomes 1 and 11 was found to co-segregate with the disorder in a large pedigree. DISC1 was one of several genes affected by the translocation and while the precise function of the gene is not known, it is thought to play a role in neuronal migration. The location of the breakpoint within DISC1 predicts that the translocation leads to impaired DISC1 protein expression.
Building on previous studies linking the DISC1 gene to schizophrenia, researchers from the University of Aberdeen have found that several markers in the gene are associated with increased risk for the disorder. In an article published in the current issue of the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Feng Zhang and colleagues genotyped multiple single nucleotide polymorphism (SNP) and microsatellite markers in a large Scottish case-control sample. They identified two SNPs and one microsatellite that show significant association with schizophrenia. The strongest association was found with a haplotype of two SNPs (rs751229 and rs3738401), located at the 5' end of the gene. The C-A haplotype of these SNPs increased the risk of developing schizophrenia by five times in their sample.
Whilst these findings are in broad agreement with several other genetic studies on DISC1, there are differences in terms of the precise patterns of association. The authors conclude that their data further implicates DISC1 as a risk factor for schizophrenia in the general population, and that an intensive screen of the gene for causative functional variants in is needed.
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