title: Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder.
abstract: Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. Although the causes of ADHD are unknown, dopaminergic, serotonergic and nor-adrenergic pathways have been strongly implicated. Monoamine Oxidase A (MAOA) is involved in the degradation of all three of these neurotransmitters and therefore has been suggested as a strong candidate gene for ADHD. Animal and human studies have implicated MAOA and 5-HT in impulsive and aggressive behavior. We therefore additionally postulated that MAOA might be associated with a subtype of ADHD where aggressive and impulsive features are especially prominent. We have tested this hypothesis by genotyping two polymorphisms (the 30-bp VNTR in the promoter and the Fnu4HI 941T-->G) in MAOA that are associated with altered MAOA function. Our sample consisted of 171 British Caucasian children 6-16 years of age fulfilling DSM-III R, DSM-IV or ICD-10 criteria for ADHD/Hyperkinetic Disorder. Using case control analysis and then the TDT, no association was found between these two MAOA polymorphisms and ADHD. Case control analysis of the VNTR showed an association with a subgroup of children with comorbid conduct problems (OR = 2.0, 95% CI = 1.09, 3.5), and TDT analysis indicated a statistical trend toward association. Our findings highlight the importance of phenotype definition and the need for the MAOA VNTR to be further examined.
authors.affiliation: Department of Psychologycal Medicine, University of Wales College of Medicine, Cardiff, United Kingdom.
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Lawson
authors.forename: Darko
authors.initials: D
authors.lastname: Turic
authors.forename: Kate
authors.initials: K
authors.lastname: Langley
authors.forename: Helen M
authors.initials: HM
authors.lastname: Pay
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Govan
authors.forename: Nadine
authors.initials: N
authors.lastname: Norton
authors.forename: Marian L
authors.initials: ML
authors.lastname: Hamshere
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Anita
authors.initials: A
authors.lastname: Thapar
mesh_terms: D000293:Adolescent; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D004247:DNA / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D018598:Minisatellite Repeats / Q000235:genetics; D008995:Monoamine Oxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D004247:DNA; D008995:Monoamine Oxidase