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 childhood characterized by inattention, excessive motor activity, impulsivity, and distractibility. It is associated with serious disability in children, adolescents and adults. 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. 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 DAT1 (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 '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.
Daly
G
G
Department of Psychiatry, Trinity College Dublin, Ireland.
Hawi
Z
Z
Fitzgerald
M
M
Gill
M
M
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D050483:Dopamine Plasma Membrane Transport Proteins; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009679:Nuclear Family; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D050641:Receptors, Dopamine D5; D012306:Risk
D002352:Carrier Proteins; C493605:DRD5 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017447:Receptors, Dopamine D1; C493214:SLC6A3 protein, human; D050641:Receptors, Dopamine D5; D004299:Dopamine beta-Hydroxylase