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

Research output: Contribution to journalArticleResearchpeer-review

62 Citations (Scopus)

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

Cite this

Domschke, Katharina ; Sheehan, Karen ; Lowe, Naomi ; Kirley, Aiveen ; Mullins, Celine ; O'Sullivan, Roderick ; Freitag, Christine ; Becker, Tim ; Conroy, Judith ; Fitzgerald, Michael ; Gill, Michael ; Hawi, Ziarih. / 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. In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2005 ; Vol. 134 B, No. 1. pp. 110-114.
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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.",
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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. / Domschke, Katharina; Sheehan, Karen; Lowe, Naomi; Kirley, Aiveen; Mullins, Celine; O'Sullivan, Roderick; Freitag, Christine; Becker, Tim; Conroy, Judith; Fitzgerald, Michael; Gill, Michael; Hawi, Ziarih.

In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Vol. 134 B, No. 1, 05.04.2005, p. 110-114.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Association analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample

T2 - Preferential transmission of the MAO-A 941G allele to affected children

AU - Domschke, Katharina

AU - Sheehan, Karen

AU - Lowe, Naomi

AU - Kirley, Aiveen

AU - Mullins, Celine

AU - O'Sullivan, Roderick

AU - Freitag, Christine

AU - Becker, Tim

AU - Conroy, Judith

AU - Fitzgerald, Michael

AU - Gill, Michael

AU - Hawi, Ziarih

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N2 - 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.

AB - 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.

KW - Attention deficit hyperactivity disorder

KW - Monoamine oxidase A

KW - Monoamine oxidase B

KW - TDT

KW - X-chromosome

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DO - 10.1002/ajmg.b.30158

M3 - Article

VL - 134 B

SP - 110

EP - 114

JO - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

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