Association analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample: Preferential transmission of the MAO-A 941G allele to affected children

Katharina Domschke, Karen Sheehan, Naomi Lowe, Aiveen Kirley, Celine Mullins, Roderick O'Sullivan, Christine Freitag, Tim Becker, Judith Conroy, Michael Fitzgerald, Michael Gill, Ziarih Hawi

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Abstract

Pharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of attention deficit hyperactivity disorder (ADHD). Monoamine oxidases A and B (MAO-A and MAO-B) degrade biogenic amines such as dopamine and serotonin and thereby control the levels of these neurotransmitters in the central nervous system. We examined four polymorphisms in the MAO-A gene (30 bp promoter VNTR, CA microsatellite in intron 2, 941G/T SNP in exon 8, and A/G SNP in intron 12) as well as two markers in the MAO-B gene (CA microsatellite in intron 2 and T/C SNP in intron 13) for association with ADHD in an Irish sample of 179 nuclear families. TDT analysis of the examined MAO-A markers revealed a significant association of the more active MAO-A 941G allele with the disorder (χ2 = 5.1, P = 0.03, OR =1.7). In addition, haplotype analysis revealed a significantly increased transmission of a haplotype consisting of the shorter allele of the promoter VNTR (allele 1), the 6-repeat allele of the CA microsatellite and the G-allele of the 941G/T SNP (famhap global statistic 34.54, F = 0.01) to ADHD cases. No significant distortion in the number of transmitted alleles was observed between the two examined MAO-B polymorphisms and ADHD. These findings suggest the importance of the 941G/T MAO-A polymorphism in the development of ADHD at least in the Irish population.

Original languageEnglish
Pages (from-to)110-114
Number of pages5
JournalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume134 B
Issue number1
DOIs
Publication statusPublished - 5 Apr 2005
Externally publishedYes

Keywords

  • Attention deficit hyperactivity disorder
  • Monoamine oxidase A
  • Monoamine oxidase B
  • TDT
  • X-chromosome

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