Meta-analysis of family-based association studies between the dopamine transporter gene and attention deficit hyperactivity disorder

Psychiatr Genet. 2005 Mar;15(1):53-9. doi: 10.1097/00041444-200503000-00009.

Abstract

Introduction: Molecular genetic research has mainly focused on the D4 dopamine receptor (DRD4) and the dopamine transporter (DAT) genes in attention-deficit hyperactivity disorder (ADHD). A recent meta-analysis showed that the DRD4 gene has a significant role in the vulnerability to ADHD.

Objectives: With an equal number of positive and negative association studies between the 10-repeat of the DAT gene and ADHD, a meta-analysis is required for this other candidate gene.

Methods: We re-analysed the 13 published family-based association studies between ADHD and the DAT gene. Following recent recommendations, different biases were specifically assessed, such as the sample-size effect and the time effect.

Results: The meta-analysis showed no significant association between ADHD and the DAT gene (P = 0.21), but an important between-samples heterogeneity (P = 0.0009). Odds ratios above 1 are mostly observed in studies with a small number of informative transmissions, and decrease with larger sample size.

Conclusions: Contrary to what was found for the DRD4 gene, the 10-repeat allele of the DAT gene has at most a minor role in the genetic susceptibility of ADHD. The different biases detected herein probably explain the initial impression of a significant impact of the DAT gene on hyperactivity.

Publication types

  • Meta-Analysis

MeSH terms

  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Confidence Intervals
  • Databases, Factual
  • Dopamine Plasma Membrane Transport Proteins
  • Family*
  • Humans
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins / genetics*
  • Nerve Tissue Proteins / genetics*
  • Odds Ratio
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D4

Substances

  • DRD4 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptors, Dopamine D2
  • SLC6A3 protein, human
  • Receptors, Dopamine D4