Identification and functional characterisation of a novel dopamine beta hydroxylase gene variant associated with ADHD

Janette Tong, Leigh-Anne McKinley, Tarrant Cummins, Beth Johnson, Natasha Matthews, Alasdair Vance, Helen Heussler, Michael Gill, Lindsey Kent, Mark Belgrove, Ziarih Hawi

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Abstract

Dysregulation in neurotransmitter signalling has been implicated in the aetiology of ADHD. Polymorphisms of the gene encoding dopamine beta hydroxylase (DBH), a key player in catecholamine signalling, have been shown to be associated with increased risk for ADHD. Previous genetic studies of ADHD have reported associations with a range of DBH gene variants (rs2519152, rs1611115, rs1108580 and rs6271) however small sample sizes have led to inconsistency. Here we conducted TDT analysis in a large ADHD sample of 794 nuclear families to re-examine the relationship between DBH and ADHD.
Although we did not replicate associations of rs2519152 and rs1611115 with ADHD, we identified a significant association with rs129882 (pcorrected = 0.02). Further, gene reporter assays of DBH rs129882 showed a significant impact of the ADHD-associated C allele on luciferase expression in a human neuroblastoma cell line, SH-SY5Y. These data demonstrate for the first time that a DBH gene variant which confers risk to ADHD is also associated with reduced in vitro gene expression.

Original languageEnglish
Number of pages9
JournalWorld Journal of Biological Psychiatry
Early online date15 May 2015
DOIs
Publication statusPublished - 2015

Keywords

  • Attention Deficit Disorder with Hyperactivity
  • Genetics
  • Gene expression
  • DBH
  • Polymorphism

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