The DRD2 TaqI polymorphism and symptoms of attention deficit hyperactivity disorder.

The relationship of the DRD2 TaqI-A1 allele to hyperactive/impulsive and inattentive symptoms of attention deficit hyperactivity disorder (ADHD) in children 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 for both traits in an analysis of all children. The heritability from the DRD2 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 controls. In this smaller sample, although the direction of the effect was the same as that in the whole sample, the genotypic differences failed to reach conventional significance levels and the effect sizes were smaller (h2 = 1.62% and 0.79%, respectively). Furthermore, a genotype relative risk test of children who had questionnaire-based diagnoses of ADHD also failed to yield evidence of either association or linkage. Given that the A1 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.

Dopamine DRD4 receptor polymorphism and attention deficit hyperactivity disorder.

A polymorphism in the dopamine receptor 4 gene (DRD4) has been related to novelty seeking, Tourette's syndrome, and attention deficit hyperactivity disorder (ADHD). The variability is in a 48-bp repeat in exon 3 of the gene (a transmembrane region). This study examined the relation of the 7-repeat (i.e., high-risk) allele to questionnaire-based diagnoses of ADHD (both combined type and inattentive type). Several positive findings were obtained for ADHD-inattentive type. In an association test, the 7-repeat allele occurred more frequently in children with ADHD-inattentive type than in control children. In genetically discordant sibling pairs, the sibling with a greater number of 7-repeat alleles displayed more inattentive symptoms than his/her co-sibling with fewer 7-repeat alleles. For ADHD-combined type, the 7-repeat allele frequency was greater than that in the control sample. However, a quantitative transmission disequilibrium test yielded no significant linkage of the 7-repeat allele with hyperactive-impulsive symptoms. A categorical TDT yielded no significant findings, but the number of transmissions was small, especially for ADHD-inattentive type.