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Related Experiment Videos

Collaborative analysis of DRD4 and DAT genotypes in population-defined ADHD subtypes.

Richard D Todd1, Hongyan Huang, Susan L Smalley

  • 1Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. toddr@psychiatry.wustl.edu

Journal of Child Psychology and Psychiatry, and Allied Disciplines
|September 24, 2005
PubMed
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Reanalyzing attention deficit hyperactivity disorder (ADHD) studies with population-based subtypes revealed a significant association between the DAT gene polymorphism and severe combined ADHD. This approach may clarify inconsistent findings in candidate gene association studies.

Area of Science:

  • Genetics
  • Neuroscience
  • Psychiatry

Background:

  • Variability in attention deficit hyperactivity disorder (ADHD) candidate gene studies may stem from genetically heterogeneous ADHD presentations.
  • Current diagnostic criteria (DSM-IV) might group distinct ADHD subtypes, complicating genetic association findings.

Purpose of the Study:

  • To investigate if population-based ADHD subtypes, identified through latent class analysis, can reconcile inconsistent results in gene association studies.
  • To re-examine previous studies on DRD4 and DAT genes in relation to ADHD subtypes.

Main Methods:

  • Reanalysis of three prior studies that found no significant associations between DRD4/DAT genes and DSM-IV ADHD.
  • Application of population-based and DSM-IV defined ADHD subtypes for the reanalysis.

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Main Results:

  • No significant associations were observed for DRD4 or DAT polymorphisms when using DSM-IV ADHD subtypes.
  • A significant association emerged between the 3' DAT VNTR polymorphism and population-defined severe combined ADHD (OR=1.25, p=.01).
  • A marginally significant association was found between the 7-repeat DRD4 allele and population-defined severe combined ADHD.

Conclusions:

  • Employing population-based ADHD subtypes can potentially resolve discrepancies in candidate gene association studies.
  • Latent class analysis-defined subtypes offer a more refined approach to understanding the genetic underpinnings of ADHD heterogeneity.