Linkage disequilibrium analysis of the dopamine beta-hydroxylase gene in persistent attention deficit hyperactivity disorder

Numerous family, twin and adoption studies have reported a strong genetic component for attention deficit hyperactivity disorder (ADHD). In addition, an extensive amount of literature has implicated abnormalities of the dopaminergic system. In view of this evidence, genes that influence dopaminergic transmission have become prime candidates for molecular genetic investigations of ADHD. There are currently three studies (Daly et al., 1999; Roman et al., 2002; Wigg et al., 2002) that have found an association between the dopamine beta-hydroxylase gene (DBH) TaqI 2 allele and childhood ADHD. As such, we tested for association of the DBH TaqI 2 allele in two independent samples of patients With the persistent variant of ADHD. These consisted of 97 nuclear families, and 112 adult cases with controls carefully matched according to gender, age and ethnicity. Transmission Disequilibrium Test analysis revealed weak over-transmission of the 2 allele (35 transmissions versus 27 non-transmissions; chi(2) = 1.03, 1 degree of freedom, P = 0.31). The case-control sample did not support previous findings since the 2 allele was more frequent in our control sample (137 versus 116; chi(2) = 3.63, 1 degree of freedom, P = 0.057). Taken together, these results do not provide support for a role of the DBH TaqI marker in our persistent ADHD samples. (C) 2004 Lippincott Williams Wilkins.