Elsevier

Biological Psychiatry

Volume 57, Issue 7, 1 April 2005, Pages 696-701
Biological Psychiatry

Original articles
Bipolar disorder and polymorphisms in the dysbindin gene (DTNBP1)

https://doi.org/10.1016/j.biopsych.2005.01.018Get rights and content

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.

Section snippets

Subjects

All subjects in these studies were Caucasian and of UK origin and provided written informed consent to participate in genetic studies. Protocols and procedures were approved by relevant ethical review panels, including the UK West Midlands Multisite Regional Ethics Committee and the South Birmingham Local Research Ethics Committee.

Bipolar probands

All the cases used met DSM-IV (American Psychiatric Association 1994) criteria for bipolar I disorder and were recruited through mental health services in England and

Results

The control individuals were genotyped in two waves, one typed with our schizophrenia sample (n = 711) and reported in Williams et al (2004) and the others typed with the bipolar sample. Duplicate samples were typed and allele coding verified. There were no significant deviations from Hardy-Weinberg equilibrium in neither the separate control sets nor in the pooled control set. The allele frequencies for each of the 3 SNPs showed no significant difference between the two control sets. Further,

Discussion

In a large, well-characterized, UK Caucasian bipolar disorder case-control sample we have examined the 3 SNPs (P1655 (rs2619539), P1635 (rs3213207) and SNP A (rs2619538)) that previously gave the strongest association within our own schizophrenia case-control sample - sampled from the same UK Caucasian population and using similar recruitment and assessment methodology (Williams et al 2004).We found no evidence for association between this 3-locus haplotype in the DTNBP1 gene and bipolar

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    This study was supported by grants from the Wellcome Trust and the United Kingdom Medical Research Council.

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