The relationship of the DRD2 Taql-A1 allele to hyperactive/impulsive and in
attentive symptoms of attention deficit hyperactivity disorder (ADHD) in ch
ildren and adolescents was examined in a sample of clinic-referred children
and their siblings, and control children and their siblings (n = 236). The
contribution of genetic dominance and additivity to mean differences among
the A2A2, A1A2, and A1A1 genotypes was estimated using structural equation
modeling. The effect of genetic additivity was statistically significant f
or both traits in an analysis of all children. The heritability from the DR
D2 locus was estimated at 4.27% for hyperactive-impulsive symptoms and 2.12
% for inattentive symptoms. Children with the A2A2 genotype had the highest
mean level of symptoms. To control for any possible effects of population
stratification, this analysis was repeated with parental genotypes as contr
ols. In this smaller sample, although the direction of the effect was the s
ame as that in the whole sample, the genotypic differences failed to reach
conventional significance levels and the effect sizes were smaller (h(2) =
1.62% and 0.79%, respectively). Furthermore, a genotype relative risk test
of children who had questionnaire-based diagnoses of ADHD also failed to yi
eld evidence of either association or linkage. Given that the Al allele was
expected to be the high risk allele, and that results were non-significant
in tests that controlled for population heterogeneity, we doubt that this
DRD2 polymorphism influences symptoms of ADHD in childhood.