The DTNBP1 (dysbindin) gene contributes to schizophrenia, depending on family history of the disease.
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.
Van Den Bogaert
Ann
A
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Schumacher
Johannes
J
Schulze
Thomas G
TG
Otte
Andreas C
AC
Ohlraun
Stephanie
S
Kovalenko
Svetlana
S
Becker
Tim
T
Freudenberg
Jan
J
Jönsson
Erik G
EG
Mattila-Evenden
Marja
M
Sedvall
Göran C
GC
Czerski
Piotr M
PM
Kapelski
Pawel
P
Hauser
Joanna
J
Maier
Wolfgang
W
Rietschel
Marcella
M
Propping
Peter
P
Nöthen
Markus M
MM
Cichon
Sven
S
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
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins