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


OBJECTIVE
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.
Purper-Ouakil
D
D
CHU Robert Debré (AP-HP, Paris VII), Paris, France.
Wohl
M
M
Mouren
M C
MC
Verpillat
P
P
Adès
J
J
Gorwood
P
P
D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D016001:Confidence Intervals; D016208:Databases, Factual; D050483:Dopamine Plasma Membrane Transport Proteins; D005190:Family; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016017:Odds Ratio; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4
C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4