Confirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism

Abstract
Attention deficit hyperactivity disorder (ADHD) is a common condition of childhood the symptoms of which include inattention, excessive motor activity, inpulsivity and distractibility. It is strongly familial1 and twin2 and adoption studies3,4 suggest that the familiality is due, at least in part, to shared genes. Gillis et al2 found concordance rates in ADHD for MZ and DZ twins of 81% and 29% respectively. Stimulant drugs (eg, methylphenidate) are effective in the treatment of ADHD5 and inhibit the dopamine transporter. This has led to the development of a hypodopaminergic hypothesis for the disease6. Cook et al7 examined a 3′ variable number of tandem repeat (VNTR) polymorphism at the dopamine transporter gene (DAT1) in a sample of 49 ADHD patients and their parents, using the haplotype relative risk (HRR) method. They found a significant association (χ2 = 7.29, 1 d.f., P = 0.007) between ADHD and the 480-bp DAT1 VNTR allele. The authors stressed the importance of independent replication and we have achieved this in a study of 40 probands and their parents, using the same robust HRR method. As in the study of Cook et al7 we found that the 480-bp allele was preferentially transmitted to ADHD probands (χ2 = 6.07, 1 d.f., P = 0.014).