Abstract
Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral problem afflicting 5–10% of children and adolescents and persisting into adulthood in 30–50% or more of cases.1,2 Family, twin, and adoption studies suggest genetic factors contribute to ADHD and symptoms of inattention, impulsivity, and hyperactivity.3–5 Because stimulant intervention is effective in reducing ADHD symptoms in about 70–80% of cases, molecular genetic investigations of genes involved in dopamine regulation are currently underway by many groups.6–8 In a case control study of the dopamine D4 receptor gene (DRD4) and ADHD, La Hoste and colleagues9 found an increase of a 7-repeat variant of a 48-bp VNTR in exon 310 among ADHD subjects compared to controls. Swanson and colleagues11 replicated this finding in a sample of 52 ADHD probands and their biological parents using a haplotype relative risk analysis. Here, we describe linkage investigations of the VNTR and ADHD in affected sibling pair (ASP) families and singleton families using both the transmission disequilibrium test (TDT)12 and a mean test of identity-by-descent (IBD) sharing. Using the TDT in the total sample, the 7 allele is differentially transmitted to ADHD children (P = 0.03) while the mean test revealed no evidence of increased IBD sharing among ASPs. In the current sample, the 7 allele attributes a 1.5-fold risk for developing ADHD over non-carriers of the allele estimated under a model described by Risch and Merikangas.13
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Smalley, S., Bailey, J., Palmer, C. et al. Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder. Mol Psychiatry 3, 427–430 (1998). https://doi.org/10.1038/sj.mp.4000457
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.mp.4000457
Keywords
This article is cited by
-
Dopamine Receptor Expression and the Pathogenesis of Attention-Deficit Hyperactivity Disorder: a Scoping Review of the Literature
Current Developmental Disorders Reports (2022)
-
DRD4 48 bp multiallelic variants as age-population-specific biomarkers in attention-deficit/hyperactivity disorder
Translational Psychiatry (2020)
-
Underlying Mechanisms and Trajectory of Comorbid ADHD and Eating Disorders: Proposing an Innovative Systems Framework for Informing Research
International Journal of Mental Health and Addiction (2016)
-
Structural signatures of DRD4 mutants revealed using molecular dynamics simulations: Implications for drug targeting
Journal of Molecular Modeling (2016)
-
Noradrenergic versus dopaminergic modulation of impulsivity, attention and monitoring behaviour in rats performing the stop-signal task
Psychopharmacology (2013)