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 had a diagnosis of schizophrenia (n = 441) or schizoaffective disorder (n = 47).


METHODS
We genotyped eight single nucleotide polymorphisms within the gene, four of which had 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 (4% 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.
Kirov
George
G
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, United Kingdom.
Ivanov
Dobril
D
Williams
Nigel M
NM
Preece
Anna
A
Nikolov
Ivan
I
Milev
Radoi
R
Koleva
Svetlinka
S
Dimitrova
Albena
A
Toncheva
Draga
D
O'Donovan
Michael C
MC
Owen
Michael J
MJ
D002031:Bulgaria / Q000208:ethnology; D002352:Carrier Proteins / Q000235:genetics*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D010290:Parents; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins