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Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD)

Molecular Psychiatry volume 5, pages 531–536 (2000)Cite this article

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental disorder. Evidence from twin, adoption, and family studies provide support for a genetic contribution to the etiology of ADHD. Several candidate gene studies have identified an association between a 7-repeat variant in exon 3 of the dopamine 4 receptor gene (DRD4) and ADHD. However, in spite of the positive reports finding association of the exon 3 VNTR with ADHD, several other polymorphisms within DRD4 have been identified that conceivably could contribute to risk for ADHD. Recently, another common polymorphism of the DRD4 gene has been described involving a 120-bp repeat element upstream of the 5′ transcription initiation site. In this report, we describe results of analysis of the DRD4 120-bp repeat promoter polymorphism in a sample of 371 children with ADHD and their parents, using the transmission disequilibrium test (TDT). Results showed a significant preferential transmission of the 240-bp (long) allele with ADHD. Exploratory analyses of the Inattentive phenotypic subtype of ADHD strengthened the evidence for linkage. These data add further support for the role of DRD4 variants conferring increased risk for ADHD, and imply that additional studies of DRD4 and other related genes are needed.

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Acknowledgements

This paper is dedicated to the memory of Dennis P Cantwell, MD. The authors also extend their appreciation to the families for their participation. The helpful contributions of T Kim, J NewDelman, E Gordon, E Carr, E Cantwell, and A Woodward are gratefully appreciated. Some of the results of the paper were obtained with the use of SAGE, which is supported by a US PHS Service Resource Grant (P41 RR03655) from the National Center for Research Resources. The project was supported by NIH grant MH 58277 (SLS) and the UCLA Tourette Syndrome Research Fund (JTM).

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Authors and Affiliations

  1. Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, Los Angeles, CA, USA

    J T McCracken, S L Smalley, J J McGough & M Del'Homme

  2. UCLA Neuropsychiatric Institute, UCLA School of Medicine, Los Angeles, CA, USA

    J T McCracken, S L Smalley, J J McGough, R M Cantor, A Liu & S F Nelson

  3. Mental Retardation Research Center, UCLA School of Medicine, Los Angeles, CA, USA

    J T McCracken & S L Smalley

  4. Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA

    S L Smalley & R M Cantor

  5. Department of Human Genetics, UCLA School of Medicine, Los Angeles

    L Crawford, R M Cantor & S F Nelson

  6. CA, USA

    L Crawford, R M Cantor & S F Nelson

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  1. J T McCracken
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  2. S L Smalley
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Correspondence to J T McCracken.

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McCracken, J., Smalley, S., McGough, J. et al. Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD). Mol Psychiatry 5, 531–536 (2000). https://doi.org/10.1038/sj.mp.4000770

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  • DOI: https://doi.org/10.1038/sj.mp.4000770

Keywords

  • attention deficit hyperactivity disorder
  • ADHD
  • dopamine
  • DRD4
  • genetics
  • neuropsychiatric genetics

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