Bipolar disorder and polymorphisms in the dysbindin gene (DTNBP1)

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Abstract

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. © 2005 Society of Biological Psychiatry.

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Raybould, R., Green, E. K., MacGregor, S., Gordon-Smith, K., Heron, J., Hyde, S., … Craddock, N. (2005). Bipolar disorder and polymorphisms in the dysbindin gene (DTNBP1). Biological Psychiatry, 57(7), 696–701. https://doi.org/10.1016/j.biopsych.2005.01.018

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