Abstract
Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. Although the causes of ADHD are unknown, dopaminergic, serotonergic and noradrenergic 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 84-89 |
| Number of pages | 6 |
| Journal | American Journal of Medical Genetics - Neuropsychiatric Genetics |
| Volume | 116 B |
| Issue number | 1 |
| State | Published - Jan 1 2003 |
| Externally published | Yes |
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Keywords
- Attention deficit hyperactivity disorder
- Conduct disorders
- Hyperkinetic disorder
- Impulsive aggressive behavior
- Monoamine oxidase A
ASJC Scopus subject areas
- Genetics(clinical)
- Neuropsychology and Physiological Psychology
- Neuroscience(all)
Cite this
Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder. / 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.
In: American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol. 116 B, No. 1, 01.01.2003, p. 84-89.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder
AU - Lawson, Deborah C.
AU - Turic, Darko
AU - Langley, Kate
AU - Pay, Helen M.
AU - Govan, Catherine F.
AU - Norton, Nadine
AU - Hamshere, Marian L.
AU - Owen, Michael J.
AU - O'Donovan, Michael C.
AU - Thapar, Anita
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. Although the causes of ADHD are unknown, dopaminergic, serotonergic and noradrenergic 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.
AB - Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. Although the causes of ADHD are unknown, dopaminergic, serotonergic and noradrenergic 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.
KW - Attention deficit hyperactivity disorder
KW - Conduct disorders
KW - Hyperkinetic disorder
KW - Impulsive aggressive behavior
KW - Monoamine oxidase A
UR - http://www.scopus.com/inward/record.url?scp=0041324737&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0041324737&partnerID=8YFLogxK
M3 - Article
VL - 116 B
SP - 84
EP - 89
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
SN - 1552-4841
IS - 1
ER -