Objective: There is considerable evidence supporting a genetic component in
the etiology of attention-deficit/hyperactivity disorder (ADHD). Because s
timulant medications act primarily on the dopaminergic system, dopamine sys
tem genes are prime candidates for genetic susceptibility factors for ADHD.
Previous studies by several groups have observed a significant association
of ADHD and an allele with 7 copies of the 48 base pair repeat in the thir
d exon of the dopamine D4 receptor. Method: The authors sought to replicate
these previous findings by collecting an independent sample of families fr
om Toronto, Ontario, Canada, and confirming this finding in an expanded sam
ple of ADHD families collected from Irvine, California. Using the transmiss
ion disequilibrium test (TDT), the authors tested for biased transmission o
f the 7-repeat allele at the exon III polymorphism of the dopamine D4 recep
tor locus in these samples of ADHD subjects. Results: Biased transmission o
f the 7-repeat allele from parents to ADHD probands and their affected sibl
ings was observed in the 2 new samples of families collected in Toronto and
irvine (TDT chi (2) = 2.711, 1 df, one-sided p Value = .050) and for these
samples combined with the 52 families previously reported from Irvine (TDT
chi (2) = 6.428, 1 df, one-sided p value = .006). Conclusions: The results
of this study further support the possibility of a role of the dopamine D4
receptor locus in ADHD.