Study Report
Basic Info
Reference |
Asherson P, 200717403983
|
Citation |
Asherson P., Brookes K., Franke B., Chen W., Gill M., Ebstein R. P., Buitelaar J., Banaschewski T., Sonuga-Barke E., Eisenberg J., Manor I., Miranda A., Oades R. D., Roeyers H., Rothenberger A., Sergeant J., Steinhausen H. C. and Faraone S. V. (2007) "Confirmation that a specific haplotype of the dopamine transporter gene is associated with combined-type ADHD." Am J Psychiatry, 164(4): 674-7.
|
Study Design |
family-based |
Study Type |
Candidate-gene association study |
Sample Size |
1,159 Trios |
Predominant Ethnicity |
Caucasian |
Population |
Belgium, Germany, the Netherlands, Ireland, Israel, Spain, Switzerland, United Kingdom |
Gender |
86.6% of the probands were male |
Age Group |
Children/Adolescents
:
aged 5-17 years
|
Detail Info
Summary |
The primary purpose of this study was to confirm the association of a specific haplotype of the dopamine transporter gene and ADHD, which could be one source of the heterogeneity seen across published studies. The authors previously reported the association of ADHD with a subgroup of chromosomes containing specific alleles of two variable-number tandem repeat polymorphisms within the 3' untranslated region and intron 8 of the dopamine transporter gene. They now report on this association in a sample of ADHD combined-type probands. The original observations were confirmed, with an overall odds ratio of 1.4 across samples. These data challenge results of meta-analyses suggesting that dopamine transporter variation does not have an effect on the risk for ADHD, and they indicate that further investigation of functional variation in the gene is required. |
Total Sample |
The final sample used in this study consisted of 998 families containing a total of 1,159 DSM-IV combined-type ADHD probands. DNA from both parents was available for 82.6% of probands (N=957) and from one parent for 13.8% (N=160). 53.4% (N=620) had comorbid oppositional defiant disorder, and 24.3% (N=282) had conduct disorder; and 72.9% (N=845) were receiving medication for ADHD at the time of the research evaluations. |
Sample Collection |
the sample consists of European Caucasian subjects recruited from 11 specialist clinics in eight countries: Belgium, Germany, the Netherlands, Ireland, Israel, Spain, Switzerland, and the United Kingdom. |
Diagnosis Description |
Entry criteria for probands were a clinical diagnosis of DSM-IV combined-subtype ADHD and having one or more full siblings available for ascertainment of clinical information and DNA collection. Exclusion criteria applying to both probands and siblings included autism, epilepsy, IQ<70, brain disorders, and any genetic or medical disorder associated with externalizing behaviors that might mimic ADHD. A standardized algorithm was applied to data from the Parent Account of Childhood Symptoms, a semistructured investigator-based interview developed to provide objective measures of child behavior, to derive each of the 18 DSM-IV ADHD items. |
Analysis Method |
analysis was conducted with the transmission disequilibrium test implemented in the software application UNPHASED. |
Result Description |
Overall they find global evidence for association with the 3'UTR VNTR, the intron 8 VNTR, and the haplotype of the two markers. Examination of the allele-specific associations shows that for the individual markers, it is the 10-repeat and six-repeat alleles that are associated with risk for ADHD. More specifically, only the 10-6 combination is overtransmitted to ADHD offspring, whereas all other haplotype combinations are undertransmitted (haplotype-specific P-value=0.002, odds ratio=1.27), confirming the previous observation of a haplotype-specific association. The only possible exception is the observation in this sample that the rare nine-repeat allele from the intron 8 VNTR might also be overtransmitted to affected offspring. |
Other variant reported by this study (count: 2)
Variant Name |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
SLC6A3 intron8 VNTR |
|
|
TDT P-value=0.0132 for intron8 VNTR; 5R: TDT P-value=0.007, ......
TDT P-value=0.0132 for intron8 VNTR; 5R: TDT P-value=0.007, OR=0.81; 6R: TDT P-value=0.03, OR=1.19; 9R: TDT P-value=0.03, OR=2.2
More...
|
global evidence for association with the intron 8 VNTR; 5R, 6R and 9R were associated with risk for ADHD |
Significant
|
SLC6A3 3'-UTR VNTR |
|
|
TDT P-value=0.0186 for 3'UTR VNTR; 10R: TDT P-value=0.010, O......
TDT P-value=0.0186 for 3'UTR VNTR; 10R: TDT P-value=0.010, OR=0.21; 9R: TDT P-value=0.005, OR=0.81
More...
|
global evidence for association with the 3'UTR VNTR; 9R and 10R were associated with risk for ADHD |
Significant
|
Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
SLC6A3 |
haplotype-specific P-value=0.002, OR=1.27. VNTR polymorphism......
haplotype-specific P-value=0.002, OR=1.27. VNTR polymorphisms in its 3' UTR and intron 8 were associated with combined ADHD.
More...
|
Significant
|