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Association study of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples

Molecular Psychiatry volume 6, pages 425–428 (2001)Cite this article

Abstract

Molecular genetic studies in attention deficit hyperactivity disorder (ADHD) have focussed on candidate genes within the dopamine system, which is thought to be the main site of action of stimulant drugs, the primary pharmacological treatment of the disorder.1 Of particular interest are findings with the dopamine transporter gene (DAT1), since stimulant drugs interact directly with the transporter protein.2,3 To date, there have been eight published association studies of ADHD with a 480 base-pair allele of a variable number tandem repeat (VNTR) polymorphism in the 3′-untranslated region of the gene, five4–8 that support an association and three9–11 against. We have analysed the same VNTR marker in a dataset of UK Caucasian children and an independent dataset of Turkish Caucasian children with DSM-IV ADHD, using the transmission disequilibrium test (TDT).12 Results from the UK (χ2 = 8.97, P = 0.001, OR = 1.95), but not the Turkish sample (χ2 = 0.93, P = 0.34) support association and linkage between genetic variation at the DAT1 locus and ADHD. When considered alongside evidence from other published reports, there is only modest evidence for the association, consistent with a very small main effect for the 480-bp allele (χ2 = 3.45, P = 0.06, OR = 1.15), however we find significant evidence of heterogeneity between the combined dataset (χ2 = 22.64, df = 8, P = 0.004).

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Acknowledgements

This research was funded by a Medical Research Council (MRC) component grant to the Social Genetic Developmental Psychiatry Research Centre. The Turkish sample was collected with funds from TUBITAK, and the Eczacibasi Scientific Research Award. Control samples were collected with funds from a Wellcome Training Fellowship to SC, and UB samples were collected with funds from a Wellcome Training Fellowship to LK. JM is an MRC PhD student. Mike Gill provided data used in original publications from the Irish group for re-analysis. We wish to thank all clinicians and families who helped in this research. Particular thanks go to Dr Geoff Kewley, Dr Mark Berelowitz, Professor Peter Hill, Fiona McNicholas, Mary Cameron and Saama El Abd.

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Authors and Affiliations

  1. Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK

    S Curran, J Mill, S Richards, A Gould, L Huckett, J Sharp, C Batten, S Fernando, E Taylor & P Asherson

  2. Department of Psychiatry, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    L Kent

  3. Child and Family Health Centre, Ashurst Hospital, Southampton, SO40 7AR, UK

    M Thompson

  4. Department of Child and Adolescent Psychiatry, GKT Medical School, London, SE1 3SS, UK

    E Simonoff

  5. TUBITAK, Marmara Research Center, Research Institute for Genetic Engineering and Biotechnology, Kocaeli, Turkey

    E Tahir

  6. Marmara University School of Medicine, Developmental Neuropsychiatry Research Unit, Istanbul, Turkey

    F Ozbay & Y Yazgan

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Correspondence to P Asherson.

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Curran, S., Mill, J., Tahir, E. et al. Association study of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples. Mol Psychiatry 6, 425–428 (2001). https://doi.org/10.1038/sj.mp.4000914

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  • DOI: https://doi.org/10.1038/sj.mp.4000914

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