Bipolar disorder and polymorphisms in the dysbindin gene (DTNBP1).
BACKGROUND
Several studies support the dysbindin (dystrobrevin binding protein 1) gene (DTNBP1) as a susceptibility gene for schizophrenia. We previously reported that variation at a specific 3-locus haplotype influences susceptibility to schizophrenia in a large United Kingdom (UK) Caucasian case-control sample.


METHODS
Using similar methodology to our schizophrenia study, we have investigated this same 3-locus haplotype in a large, well-characterized bipolar sample (726 Caucasian UK DSM-IV bipolar I patients; 1407 ethnically matched controls).


RESULTS
No significant differences were found in the distribution of the 3-locus haplotype in the full sample. Within the subset of bipolar I cases with predominantly psychotic episodes of mood disturbance (n = 133) we found nominally significant support for association at this haploptype (p < .042) and at SNP rs2619538 (p = .003), with a pattern of findings similar to that in our schizophrenia sample. This finding was not significant after correction for multiple testing.


CONCLUSIONS
Our data suggest that variation at the polymorphisms examined does not make a major contribution to susceptibility to bipolar disorder in general. They are consistent with the possibility that DTNBP1 influences susceptibility to a subset of bipolar disorder cases with psychosis. However, our subset sample is small and the hypothesis requires testing in independent, adequately powered samples.
Raybould
Rachel
R
Department of Psychological Medicine, Wales College of Medicine, Cardiff University, Cardiff, Wales, UK.
Green
Elaine K
EK
MacGregor
Stuart
S
Gordon-Smith
Katherine
K
Heron
Jess
J
Hyde
Sally
S
Caesar
Sian
S
Nikolov
Ivan
I
Williams
Nigel
N
Jones
Lisa
L
O'Donovan
Michael C
MC
Owen
Michael J
MJ
Jones
Ian
I
Kirov
George
G
Craddock
Nick
N
D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003710:Demography; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D006113:United Kingdom
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins