Original articlesBipolar disorder and polymorphisms in the dysbindin gene (DTNBP1)
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
References (42)
- et al.
Polymorphisms at the G72/G30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series
Am J Hum Genet
(2003) - et al.
Strong evidence for association between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia in 488 parent-offspring trios from Bulgaria
Biol Psychiatry
(2004) - et al.
No evidence for association of the dysbindin gene [DTNBP1] with schizophrenia in an Irish population-based study
Schizophr Res
(2003) - et al.
Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families
Am J Hum Genet
(2003) - et al.
Genome scan meta-analysis of schizophrenia and bipolar disorder, part IIIBipolar disorder
Am J Hum Genet
(2003) - et al.
Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia
Am J Hum Genet
(2002) - et al.
Increased morbid risk for schizophrenia in families of in-patients with bipolar illness
Schizophr Res
(2000) Diagnostic and Statistical Manual of Mental Disorders
(1994)- et al.
The high affinity neurotensin receptor gene (NTSR1)comparative sequencing and association studies in schizophrenia
Mol Psychiatry
(2000) - et al.
Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia
Mol Psychiatry
(2002)
Association between reported education and intellectual functioning in an ethnically diverse adult psychiatric inpatient sample
J Natl Med Assoc
The Wellcome trust UK-Irish bipolar affective disorder sibling-pair genome screenfirst stage report
Mol Psychiatry
Evidence for shared susceptibility in bipolar disorder and schizophrenia
Am J Med Genet
A twin study of genetic relationships between psychotic symptoms
Am J Psychiatry
Findings in an independent sample support an association between bipolar affective disorder and the G72/G30 locus on chromosome 13q33
Mol Psychiatry
Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia
Proc Natl Acad Sci U S A
Genetics of Bipolar Disorder
J Med Genetics
The Bipolar Affective Disorder Dimension Scale (BADDS) - a dimensional scale for rating lifetime psychopathology in Bipolar spectrum disorders
BMC Psychiatry
Mathematical limits of multilocus modelsthe genetic transmission of bipolar disorder
American Journal of Human Genetics
Pedigree disequilibrium tests for multilocus haplotypes
Genet Epidemiol
A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands
Arch Gen Psychiatry
Cited by (87)
DNA Methylation and Psychiatric Disorders
2018, Progress in Molecular Biology and Translational ScienceMood disorders and parity - A clue to the aetiology of the postpartum trigger
2014, Journal of Affective DisordersCitation Excerpt :In this paper we test the hypothesis that the risk of perinatal mood episodes is greater following first pregnancies and ask whether this association: (i) holds across the mood disorder spectrum (bipolar I – BD-I, bipolar II – BD-II and recurrent major depression – RMD); (ii) is found for both episodes of high and low mood; (iii) applies to all episodes in relation to pregnancy and childbirth or is limited to those with onset in the immediate postpartum; and finally (iv) is impacted by possible confounders, such as decisions about having further children, age at pregnancy and method of delivery. Participants were drawn from 2 clinical and genetic studies of mood disorders (one on RMD and one on BD) and are described in detail elsewhere (Cohen-Woods et al., 2009; Raybould et al., 2005). In brief, participants were recruited using both systematic and non-systematic methods across the United Kingdom.
An updated overview of animal models in neuropsychiatry
2013, NeuroscienceCitation Excerpt :These studies focused on aberrant increase in the CpG DNA methylation leading to alteration in gene expression for genes involved in neurotransmission, metabolism and myelination. In one study by Mill et al., evaluating methylation profiles on major psychosis samples in the frontal cortex of postmortem brain samples, he identified several genes with methylation changes (Mill et al., 2008) that include the locus DYSBININ which has been implicated as genetic risk for developing psychosis (Straub et al., 2002; Raybould et al., 2005; Pae et al., 2007). Many of the altered genes were related to psychosis related genes involving the GABAergic neurotransmission, stress response and brain development genes (Konradi et al., 2004; Akbarian et al., 2005; Sokolov, 2007; Hashimoto et al., 2008; Karoutzou et al., 2008).
Dysbindin (DTNBP1) - A role in psychotic depression?
2011, Journal of Psychiatric ResearchCitation Excerpt :One might only speculate that – given some preliminary evidence for DTNBP1 genotype to eventually affect glutamatergic neurotransmission via reduced DTNBP1 expression (Numakawa et al., 2004; Bray et al., 2005) – psychotic depression potentially in part mediated by DTNBP1 gene variation might be particularly targetable by emerging therapeutic agents acting at the glutamatergic system (cf. Sanacora et al., 2008). Furthermore, considering reports of dysbindin gene variation to be associated with a wide continuum of mental disorders such as schizophrenia (e.g., Straub et al., 2002; Schwab et al., 2003; van den Oord et al., 2003), schizophrenia with anxiety/depression symptoms (Wirgenes et al., 2009), bipolar disorder with or without psychotic features (Raybould et al., 2005; Pae et al., 2007b), major depression (Kim et al., 2008; but: Wray et al., 2008; Zill et al., 2004), antidepressant treatment response in psychotic depression (Arias et al., 2009; Pae et al., 2007a) and presently psychotic depression, DTNBP1 variation might indeed contribute to the shared genetic susceptibility to psychotic and affective disorders (for review see Maier, 2008; Van Den Bogaert et al., 2006; Wildenauer et al., 1999), possibly via an intermediate phenotype common to both schizophrenia and affective disorders. Thus, future studies could focus on investigating the impact of DTNBP1 variation on neuropsychological profiles, e.g., cognitive function and its relation to cortisol (Gomez et al., 2006; Luciano et al., 2009), or neuroimaging markers such as reduced amygdala volume (Keller et al., 2008) or prefrontal brain function (cf. Fallgatter et al., 2006, 2010) as intermediate phenotypes of potentially both psychotic and affective disorders in order to further delineate the role of dysbindin in the pathogenesis of these disorders.
Identification of high risk DISC1 protein structural variants in patients with bipolar spectrum disorder
2010, Neuroscience Letters
This study was supported by grants from the Wellcome Trust and the United Kingdom Medical Research Council.