Genetic association between schizophrenia and the DISC1 gene in the Scottish population

Several lines of evidence support the involvement of the disrupted in schizophrenia 1 (DISC1) gene in schizophrenia susceptibility, including its original identification in a schizophrenia family with a chromosome translocation, several genetic association studies, and functional characterization of the gene product. In the present study, we have genotyped multiple SNP and microsatellite markers in a large Scottish case-control sample. We identified two SNPs and one microsatellite that show significant association with schizophrenia. The strongest association is with a haplotype of SNPs rs751229 and rs3738401, located at the 5' end of the gene; the C-A haplotype of these SNPs is associated with a relative risk of schizophrenia of 5 in our population. We also observe association with a microsatellite in intron 7, but no association with markers toward the 3' end of the gene. The results are in broad agreement with those of other genetic studies, but there are differences in terms of the precise patterns of association. This analysis further strengthens the candidacy of DISC1 as a risk factor for schizophrenia in the general population, and suggests that more intensive searching for causative variants is justified. (C) 2006 Wiley-Liss, Inc.