Strong evidence for association between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia in 488 parent-offspring trios from Bulgaria

Background: The gene encoding the dystrobrevin binding protein (DTNBP1) has been implicated in the pathogenesis of schizophrenia by several association studies. We tried to replicate these findings in a sample of 488 parent-proband trios recruited in Bulgaria. Probands bad a diagnosis of schizophrenia (n = 441) or schizoaffective disorder (n = 47). Methods: We genotyped eight single nucleotide polymorphisms within the gene, four of which bad been reported in previous studies, and four identified as informative by our group through direct screening of the gene and genotyping in a sample of cases and control subjects. Results: A significant excess of transmissions was observed for two of the markers, p1635 and p1757, (p = .0009 and .0013, respectively). Analysis of two-, three-, and four-marker haplotypes produced numerous positive results, with six (4016 of the total combinations) at p < .001. Conclusions. These results provide strong support for DTNBP1 as a susceptibility gene for schizophrenia; however, different haplotypes seem to be associated in different studies.