Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD)

Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental disorder. Evidence from twin, adoption, and family stud ies provide support for a genetic contribution to the etiology of ADHD, Sev eral candidate gene studies have identified an association between a 7-repe at variant in exon 3 of the dopamine 4 receptor gene (DRD4) and ADHD. Howev er, in spite of the positive reports finding association of the exon 3 VNTR with ADHD, several other polymorphisms within DRD4 have been identified th at conceivably could contribute to risk for ADHD, Recently, another common polymorphism of the DRD4 gene has been described involving a 120-bp repeat element upstream of the 5' transcription initiation site. In this report, w e describe results of analysis of the DRD4 120-bp repeat promoter polymorph ism in a sample of 371 children with ADHD and their parents, using the tran smission disequilibrium test (TDT). Results showed a significant preferenti al transmission of the 240-bp (long) allele with ADHD, Exploratory analyses of the Inattentive phenotypic subtype of ADHD strengthened the evidence fo r linkage. These data add further support for the role of DRD4 variants con ferring increased risk for ADHD, and imply that additional studies of DRD4 and other related genes are needed.