Association of the dopamine receptor D4 (DRD4) gene 7-repeat allele with children with attention-deficit/hyperactivity disorder (ADHD): An update

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2007-04, Vol.144B (3), p.379-382
• Main Authors: Gornick, M.C., Addington, Anjene, Shaw, P., Bobb, A.J., Sharp, W., Greenstein, D., Arepalli, S., Castellanos, F.X., Rapoport, J.L.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Alleles; Attention Deficit Disorder with Hyperactivity - genetics; Biological and medical sciences; Case-Control Studies; Child; Family; Gene Frequency; genetic association; Genetic Linkage; Humans; Medical genetics; Medical sciences; Minisatellite Repeats; quantitative TDT; Receptors, Dopamine D4 - genetics; transmission disequilibrium test
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30460

Polymorphisms of the dopamine receptor D4 gene DRD4, 11p15.5, have previously been associated with attention‐deficit/hyperactivity disorder (ADHD) [Bobb et al., 2005; Am J Med Genet B Neuropsychiatr Genet 132:109–125; Faraone et al., 2005; Biol Psychiatry 57:1313–1323; Thapar et al., 2005; Hum Mol Genet 14 Spec No. 2:R275‐R282]. As a follow up to a pilot study [see Castellanos et al., 1998; Mol Psychiatry 3:431–434] consisting of 41 probands and 56 controls which found no significant association between the DRD4 7‐repeat allele in exon 3 and ADHD, a greatly expanded study sample (cases n = 166 and controls n = 282) and long term follow‐up (n = 107, baseline mean age n = 9, follow‐up mean age of n = 15) prompted reexamination of this gene. The DRD4 7‐repeat allele was significantly more frequent in ADHD cases than controls (OR = 1.2; P = 0.028). Further, within the ADHD group, the 7‐repeat allele was associated with better cognitive performance (measured by the WISC‐III) (P = 0.013–0.07) as well as a trend for association with better long‐term outcome. This provides further evidence of the role of the DRD4 7‐repeat allele in the etiology of ADHD and suggests that this allele may be associated with a more benign form of the disorder. © 2006 Wiley‐Liss, Inc.