Study Report

Basic Info
Reference |
Lawson DC, 200312497620
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Citation |
Lawson D. C., Turic D., Langley K., Pay H. M., Govan C. F., Norton N., Hamshere M. L., Owen M. J., O'Donovan M. C. and Thapar A. (2003) "Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder." Am J Med Genet B Neuropsychiatr Genet, 116B(1): 84-9.
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Study Design |
case-control and family-based |
Study Type |
Candidate-gene association study |
Sample Size |
171 families with 171 children, and 351 controls |
Predominant Ethnicity |
Caucasian |
Population |
United Kingdom |
Gender |
case-control: 123 males, 50 females in sample 1, 127 males, 51 females in sample 2; family-based: 153 males and 18 females |
Age Group |
Children/Adolescents and Adults
:
case-control: mean age 42(SD=12) years, mean age 44 (SD=12) years; family-based: 6-16 years
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Detail Info
Summary |
They therefore additionally postulated that MAOA might be associated with a subtype of ADHD where aggressive and impulsive features are especially prominent. They 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. Their 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, and TDT analysis indicated a statistical trend toward association. |
Total Sample |
The sample meeting their acceptance criteria consisted of 171 British Caucasian children (ethnicity including parents and grandparents), 153 males and 18 females between the age of 6 and 16 from 171 families with 170 available mothers (1 mother had died) and 138 fathers. Genotypes from two case control samples (combined for the analyses) were available for the 941T->G polymorphism. Sample 1 was comprised of 173 United Kingdom Caucasian control subjects, (male: n=123, female: n=50), mean age 42 (SD=12) years collected from the U.K. blood transfusion service in Wales. The second sample was ascertained in the same way from the same source and was comprised of 178 blood donor controls (male n=127, female n=51) mean age 44 (SD=12) years. Genotypes were only available for the 30 bp VNTR for the first of these two samples. |
Sample Collection |
Individuals with diagnosed or suspected ADHD were recruited from district Child and Adolescent Psychiatry and Paediatric clinics in Greater Manchester, Cheshire, Bristol, Weston-Super-Mare and South Wales, United Kingdom. Sample 1 of two case control samples was comprised of 173 United Kingdom Caucasian control subjects, collected from the U.K. blood transfusion service in Wales. The second sample was ascertained in the same way from the same source and was comprised of 178 blood donor controls. |
Diagnosis Description |
Participants were diagnosed according to ICD-10, DSM-IV, and DSM-III-R criteria. From our sample of 171 probands 55.7% of children fulfilled criteria for ICD-10 hyperkinetic disorder, 61.5% for DSM-IV combined type ADHD, 9.4% for DSM-IV inattentive subtype, 14.1% for DSM-IV hyperactive impulsive subtype and 94.3% for DSM-III-R ADHD. |
Technique |
DNA was extracted from venous blood, mouthwashes or from cheek swabs using standard procedures for 171 children. DNA samples were also obtained from both biological parents for 137 probands and from only one biological parent for 34 probands. The 941T->G polymorphism (G/T) was genotyped as described by Furlong et al. [1999]. The 30 bp VNTR was amplified using primers described by Sabol et al. [1998]. PCR products were electrophoresed on a 10% polyacrylamide gel for 2.5 hr on a 377 DNA sequencer. Raw data were analyzed using the ABI GENESCAN analysis and GENOTYPER software (Applied Biosystems, Foster City, CA). |
Analysis Method |
The data were analyzed first using case control analysis (JWoolf in-house software used for OR). The extended transmission disequilibrium test (ETDT) [Sham and Curtis, 1995] was used in the family based analysis using the statistical method of logistic regression. Because MAOA is a sex-linked gene DNA from fathers was only utilized in the analyses of female probands. |
Result Description |
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. Their findings highlight the importance of phenotype definition and the need for the MAOA VNTR to be further examined. |

Other variant reported by this study (count: 2)
Variant Name |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
MAOA exon8 941G/T |
G/T |
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allelic TDT P-value=0.80, X2(1df)=0.06 in full sa......
allelic TDT P-value=0.80, X2(1df)=0.06 in full sample, allelic TDT P-value=0.90, X2(1df)=0.02 in male probands; OR(total sample)=0.99, OR(male probands)=1.23 in case-control analysis
More...
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there was no evidence of association with ADHD using case control analysis; no preferential transmission of alleles was found in the total sample or in the male probands only |
Non-significant
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MAOA promoter VNTR |
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allelic TDT P-value=0.45, X2(1df)=0.58 in full sa......
allelic TDT P-value=0.45, X2(1df)=0.58 in full sample, allelic TDT P-value=0.25, X2(1df)=1.32 in male probands;
More...
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there was no evidence of association with ADHD using case control analysis; no preferential transmission of alleles was found in the total sample or in the male probands only |
Non-significant
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
MAOA |
there was no evidence of association between 2 polymorphisms......
there was no evidence of association between 2 polymorphisms and ADHD using case control analysis; no preferential transmission of alleles was found in the total sample or in the male probands only
More...
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Non-significant
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