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Association of the calcyon gene (DRD1IP) with attention deficit/hyperactivity disorder

Molecular Psychiatry volume 10, pages 1117–1125 (2005)Cite this article

Abstract

Attention deficit/hyperactivity disorder (ADHD) is a childhood-onset disorder characterized by marked inattention, hyperactivity and impulsivity. The dopaminergic system has been hypothesized to be involved in the development of ADHD. Positive associations have been found for the dopamine receptors D1 and D5 genes, suggesting that other genes involved in D1/D5 signalling may also contribute to ADHD. In this study, we tested the calcyon gene (DRD1IP), which encodes a brain-specific D1-interacting protein involved in D1/D5 receptors calcium signalling, for association with ADHD. The inheritance of nine polymorphisms in the calcyon gene was examined in a sample of 215 nuclear families, with 260 affected children, using the transmission/disequilibrium test. The most common haplotype, designated C1, demonstrated significant evidence for excess transmission. Quantitative trait analyses of this haplotype showed significant relationships with both the inattentive (parent's rating, P=0.006; teacher's rating, P=0.003) and hyperactive/impulsive (parent's rating, P=0.004) dimensions of the disorder. Two of the nine marker alleles included in haplotype C1, rs4838721A located ∼10 kb 5′ of the gene and rs2275723C located 10 bp upstream of the exon 5 acceptor splice site, also showed significant evidence for association when analysed individually. As these two variants are not predicted to alter calcyon function, we screened the gene exons by sequencing. No variation in the coding region was identified, suggesting that a causal variant allele resides elsewhere in a regulatory sequence of the gene. These findings support the proposed involvement of the calcyon gene in ADHD and implicate haplotype C1 as containing a risk allele.

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Acknowledgements

This work was supported by Postdoctoral Fellowships from the Hospital for Sick Children Research Training Centre (NL and VLM) and by grants from The Hospital for Sick Children Psychiatric Endowment Fund (CLB), and the Canadian Institutes of Health Research MT14336 and MOP14334 (CLB).

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Authors and Affiliations

  1. Cell and Molecular Biology Division, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada

    N Laurin, V L Misener & C L Barr

  2. Department of Psychiatry, Brain and Behaviour Programme, The Hospital for Sick Children, Toronto, ON, Canada

    J Crosbie, A Ickowicz, T Pathare, R Tannock, R Schachar & C L Barr

  3. Division of Neurology, Brain and Behaviour Programme, The Hospital for Sick Children, Toronto, ON, Canada

    W Roberts & M Malone

  4. Department of Psychiatry, Neurogenetics Section, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada

    J L Kennedy

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Correspondence to C L Barr.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Laurin, N., Misener, V., Crosbie, J. et al. Association of the calcyon gene (DRD1IP) with attention deficit/hyperactivity disorder. Mol Psychiatry 10, 1117–1125 (2005). https://doi.org/10.1038/sj.mp.4001737

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