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A family-based and case-control association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder

Molecular Psychiatry volume 5, pages 523–530 (2000)Cite this article

Abstract

Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric condition of early childhood onset characterised by marked inattention, hyperactivity and impulsiveness. Molecular genetic investigations of ADHD have found positive associations with the 480-bp allele of a VNTR situated in the 3′ untranslated region of DAT1 and allele 7 of a VNTR in exon 3 of DRD4. A number of independent studies have attempted to replicate these findings but the results have been inconsistent. We used both family-based and case control approaches to examine these polymorphisms in a sample of 137 children diagnosed with ICD-10, DSM-IV or DSM-III-R ADHD. We found no evidence of association with the DAT1 polymorphism, despite a sample size that has up to 80% power to detect a previously reported effect size. We observed a significant increase in the DRD4 7 repeat allele amongst ADHD probands (21.7%) and their parents (18.9% in mothers, 22.3% in fathers), compared to ethnically matched controls (12.8%). However TDT analysis showed no preferential transmission of allele 7 to ADHD probands.

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Acknowledgements

This study was funded by Action Research and SPARKS. We thank Kay Poulton for initial assistance with laboratory work; Nicole Perrin Trent for administrative support and all our colleagues from Child and Adolescent Psychiatry services in Greater Manchester and Cheshire, UK for referring families to the study. Finally, we are extremely grateful to all the families who participated in this study.

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Authors and Affiliations

  1. University Department of Child and Adolescent Psychiatry, Royal Manchester Children's Hospital, Manchester, M27 4HA, UK

    J Holmes, T Hever, H Fitzpatrick, A L Trumper, R Harrington & A Thapar

  2. ARC Epidemiology Unit, The University of Manchester, Manchester, M13 9PL, UK

    A Payton, J H Barrett, W Ollier & J Worthington

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

    P McGuffin

  4. Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, CF14 4XN, Wales, UK

    M Owen

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  1. J Holmes
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  2. A Payton
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  3. J H Barrett
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  4. T Hever
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  5. H Fitzpatrick
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  6. A L Trumper
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  7. R Harrington
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  8. P McGuffin
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  9. M Owen
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  10. W Ollier
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  11. J Worthington
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  12. A Thapar
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Correspondence to A Thapar.

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Holmes, J., Payton, A., Barrett, J. et al. A family-based and case-control association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder. Mol Psychiatry 5, 523–530 (2000). https://doi.org/10.1038/sj.mp.4000751

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  • DOI: https://doi.org/10.1038/sj.mp.4000751

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