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

Attention deficit hyperactivity disorder (ADHD) is a common disorder of chi ldhood 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 ha ve suggested that dopaminergic and noradrenergic systems are involved.(2) U sing a sample of affected children and their parents we have found preferen tial 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 pre vious findings for DAT1(3) (new sample one-tailed P = 0.039); dopamine-beta -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 'a ssociated' alleles at DAT1 and DBH is stronger in familial cases, RRDAT1 = 1.29 (1.04-1.59), RRDBH = 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 comp lete trios supports the HHRR analysis, with P < 0.05, for DAT1 P < 0.005 an d 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.