ADHDgene Database

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Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

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)