Examining for association between candidate gene polymorphisms in the dopamine pathway and attention-deficit hyperactivity disorder: A family-based study

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable child hood-onset psychiatric condition characterized by developmentally inappropr iate inattention, hyperactivity, and impulsiveness. The pathophysiology of ADHD is currently unknown. However, the therapeutic effects of stimulant me dication together with findings from animal and neuroimaging studies as wel l as from several molecular genetic studies of the dopamine receptor D4 gen e and dopamine transporter gene have implicated involvement of the dopamine rgic system, To test the dopaminergic hypothesis further, we have looked fo r association between ADHD and alleles of seven dopamine-related candidate genes using a family-based association approach in a sample of 150 children diagnosed with ADHD. We tested polymorphisms in genes encoding three dopam ine receptors (DRD3, DRD4, and DRD5) and four dopamine-relevant enzymes: ty rosine hydroxylase [tyrosine hydroxylase (TH)], dopamine beta hydroxylase ( DPH), catechol-O-methyltransferase (COMT), and monoamine oxidase A (MAOA), We were unable to detect a significant association with any of the polymorp hisms genotyped, although there was a trend for preferential transmission o f the DRD5 148 bp marker allele and the MAOA 122 bp marker allele, We concl ude that none of the alleles we have tested makes a major contribution to A DHD, although much larger samples are required to exclude small effects. (C ) 2001 Wiley-Liss,Inc.