Association of the dopamine beta hydroxylase gene with attention deficit hyperactivity disorder: Genetic analysis of the Milwaukee longitudinal study

Karen Müller Smith, Mark Daly, Mariellen Fischer, Constantin T. Yiannoutsos, Lorri Bauer, Russell Barkley, Bradford A. Navia

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Attention deficit hyperactivity disorder (ADHD) is a highly heritable and common disorder that partly reflects disturbed dopaminergic function in the brain. Recent genetic studies have shown that candidate genes involved in dopamine signaling and metabolism contribute to ADHD susceptibility. We have initiated genetic studies in a unique cohort of 158 ADHD and 81 control adult subjects who have been followed longitudinally since childhood in the Milwaukee study of ADHD. From this cohort, genetic analysis was performed in 105 Caucasian subjects with ADHD and 68 age and ethnicity-matched controls for the DRD4 exon 3 VNTR, the SLC6A3 (DAT1) 3′ UTR VNTR, dopamine beta hydroxylase (DBH) TaqI A polymorphism, and the DBH GT microsatellite repeat polymorphism that has been quantitatively associated with serum levels of DBH activity, but not previously studied in ADHD. Results indicate a significant association between the DBH TaqI A1 allele and ADHD (P = 0.018) with a relative risk of 1.33. The DBH GT repeat 4 allele, which is associated with high serum levels of DBH, occurred more frequently in the ADHD group than controls, but the difference did not reach statistical significance. Associations were not found with the SLC6A3 10 repeat or DRD4 7 repeat alleles. These results indicate that the DBH TaqI A allele, or another polymorphism in linkage disequilibrium with this allele, may confer increased susceptibility towards ADHD.

Original languageEnglish (US)
Pages (from-to)77-85
Number of pages9
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume119 B
Issue number1
StatePublished - May 15 2003

Keywords

  • Attention deficit hyperactivity disorder
  • Dopamine
  • Dopamine beta hydroxylase

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

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