title: The DTNBP1 (dysbindin) gene contributes to schizophrenia, depending on family history of the disease.
abstract: We have investigated the gene for dystrobrevin-binding protein 1 (DTNBP1), or dysbindin, which has been strongly suggested as a positional candidate gene for schizophrenia, in three samples of subjects with schizophrenia and unaffected control subjects of German (418 cases, 285 controls), Polish (294 cases, 113 controls), and Swedish (142 cases, 272 controls) descent. We analyzed five single-nucleotide polymorphisms (P1635, P1325, P1320, P1757, and P1578) and identified significant evidence of association in the Swedish sample but not in those from Germany or Poland. The results in the Swedish sample became even more significant after a separate analysis of those cases with a positive family history of schizophrenia, in whom the five-marker haplotype A-C-A-T-T showed a P value of.00009 (3.1% in controls, 17.8% in cases; OR 6.75; P=.00153 after Bonferroni correction). Our results suggest that genetic variation in the dysbindin gene is particularly involved in the development of schizophrenia in cases with a familial loading of the disease. This would also explain the difficulty of replicating this association in consecutively ascertained case-control samples, which usually comprise only a small proportion of subjects with a family history of disease.
authors: Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
authors: Ann
authors: A
authors: Van Den Bogaert
authors: Johannes
authors: J
authors: Schumacher
authors: Thomas G
authors: TG
authors: Schulze
authors: Andreas C
authors: AC
authors: Otte
authors: Stephanie
authors: S
authors: Ohlraun
authors: Svetlana
authors: S
authors: Kovalenko
authors: Tim
authors: T
authors: Becker
authors: Jan
authors: J
authors: Freudenberg
authors: Erik G
authors: EG
authors: Jönsson
authors: Marja
authors: M
authors: Mattila-Evenden
authors: Göran C
authors: GC
authors: Sedvall
authors: Piotr M
authors: PM
authors: Czerski
authors: Pawel
authors: P
authors: Kapelski
authors: Joanna
authors: J
authors: Hauser
authors: Wolfgang
authors: W
authors: Maier
authors: Marcella
authors: M
authors: Rietschel
authors: Peter
authors: P
authors: Propping
authors: Markus M
authors: MM
authors: Nöthen
authors: Sven
authors: S
authors: Cichon
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005787:Gene Frequency; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D044465:White People
chemical_list: D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins