Mapping susceptibility loci in attention deficit hyperactivity disorder: preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected children

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common disorder of childhood characterized by inattention, excessive motor activity, impulsivity, and distractibility. It is associated with serious disability in children, adolescents and adults.¹ The etiology of the disorder is unknown, but it has a strong genetic component. Pharmacological and biochemical studies have suggested that dopaminergic and noradrenergic systems are involved.² Using a sample of affected children and their parents we have found preferential transmission of alleles at polymorphisms at the dopamine transporter (DAT1), RR = 1.2 (1.05–1.37), P = 0.006, re-confirming and extending our previous findings for DAT1³ (new sample one-tailed P = 0.039); dopamine-β-hydroxylase (DBH), RR = 1.31 (1.09–1.56), P = 0.0027; and the dopamine D5 receptor (DRD5), RR = 1.67 (1.29–2.15), P = 0.00005. Transmission of the ‘associated’ alleles at DAT1 and DBH is stronger in familial cases, RR_DAT1 = 1.29 (1.04–1.59), RR_DBH = 1.49 (1.10–2.00), but for DRD5, transmission is stronger in non-familial cases, RR = 1.59 (1.05–2.42). TDT analysis of complete trios supports the HHRR analysis, with P < 0.05, for dat1 P < 0.005 and dbh and P < 0.01 for drd5. attributable fractions for dat1, dbh and drd5 are calculated at 0.08, 0.12 and 0.20 respectively.