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Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder
Author(s) -
Lawson Deborah C.,
Turic Darko,
Langley Kate,
Pay Helen M.,
Govan Catherine F.,
Norton Nadine,
Hamshere Marian L.,
Owen Michael J.,
O'Donovan Michael C.,
Thapar Anita
Publication year - 2002
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.10002
Subject(s) - monoamine oxidase a , attention deficit hyperactivity disorder , dopaminergic , psychology , monoamine oxidase , serotonergic , psychiatry , clinical psychology , dopamine , medicine , neuroscience , serotonin , biology , biochemistry , enzyme , receptor
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. © 2003 Wiley‐Liss, Inc.