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	Curran S, 200111443527
Citation	Curran S., Mill J., Tahir E., Kent L., Richards S., Gould A., Huckett L., Sharp J., Batten C., Fernando S., Ozbay F., Yazgan Y., Simonoff E., Thompson M., Taylor E. and Asherson P. (2001) "Association study of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples." Mol Psychiatry, 6(4): 425-8.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	66 ADHD children in the United Kingdom sample, 111 trios in the Turkish sample
Predominant Ethnicity	Caucasian
Population	United Kingdom, Turkey
Age Group	Children/Adolescents

Detail Info

Summary	They have analysed the same VNTR marker (a 480 base pair allele of a variable number tandem repeat (VNTR) polymorphism in the 3' untranslated region of the gene) in a dataset of United Kingdom Caucasian children and an independent dataset of Turkish Caucasian children with DSM-IV ADHD, using the transmission disequilibrium test (TDT). Results from the United Kingdom, but not the Turkish sample support association and linkage between genetic variation at the DAT1 locus and ADHD. When considered alongside evidence from other published reports, there is only modest evidence for the association, consistent with a very small main effect for the 480-bp allele, however they find significant evidence of heterogeneity between the combined dataset.
Total Sample	The United Kingdom sample consisted of 59 cases with the combined subtype, six the hyperactive/impulsive subtype and one the inattentive subtype of ADHD. The Turkish sample consisted of 111 complete trios with DSM-IV-ADHD combined type.
Sample Collection	The United Kingdom cases were collected at the Institute of Psychiatry (IOP) and the University of Birmingham (UB) following referral by child behavioural clinics in Southern and Mid-United Kingdom. The Turkish sample was collected at the Marmara University Medical School in Istanbul (UM) from cases attending a Neuropsychiatric clinic.
Diagnosis Description	Parents of referred cases were interviewed with a modified version of the Child Assessment Parent Interview (CAPA) and information on ADHD symptoms at school were obtained using the Teacher Conners questionnaire. Following the IOP assessments, HYPESCHEME data sheets were completed using data gathered from the research interview, teacher's questionnaire and where necessary review of case notes. HYPESCHEME diagnoses were checked against researcher applied DSM-IV criteria and discrepancies reviewed by two researchers (PA and SR). Where consensus could not be reached, cases were brought to case conference and final consensus agreement made with a senior clinical researcher (ET). In UB DSM-IV criteria were applied directly by the researcher (LK) and consensus diagnosis agreed at case conference. Diagnoses in Turkey were made following a research interview using the Kiddie-Schedule for Affective Disorders and Schizophrenia (K-SADS) with one of the child's parents and review of behavioural questionnaires including Connors parent and teacher rating scales and the Child Behavioural Checklist (CBCL) with the associated Teacher Report Form (TRF). DSM-IV criteria were applied directly by the researcher (YY) and consensus diagnosis agreed at case conference.
Technique	The 3' UTR VNTR was amplified on an MJ PTC-225 thermal cycler in a hot-start protocol involving an initial 5-min denaturing step at 95^oC, followed by 38 cycles of 93^oC for 1 min and 72^oC for 1 min. The primers used were 5'-TGT GGT GTA GGG AAC GGC CTG AG-3' and 5'-CTT CCT GGA GGT CAC GGC TCA AGG-3'. The reaction mix included 75 ng of genomic DNA, 1.5 mM MgCl₂, 20 mM dNTPs, 10 mM 10xPCR buffer and 1 unit of Taq polymerase. PCR products were run out on a 2% agarose gel.
Analysis Method	Association of the 480-bp allele of the DAT1 VNTR with ADHD was investigated using the transmission disequilibrium test (TDT). They combined available published data on the VNTR polymorphism and performed a combined TDT analysis. They performed a test of homogeneity by applying the chi-square-statistic to the table of studies against the number of transmitted and untransmitted alleles.
Result Description	Results from the United Kingdom (X²=8.97, P=0.001, OR=1.95), but not the Turkish sample (X²=0.93, P=0.34) support association and linkage between genetic variation at the DAT1 locus and ADHD. When considered alongside evidence from other published reports, there is only modest evidence for the association, consistent with a very small main effect for the 480-bp allele (X²=3.45, P=0.06, OR=1.15), however they find significant evidence of heterogeneity between the combined dataset (X²=22.64, df=8, P=0.004).

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
SLC6A3 3'-UTR VNTR		480bp allele	TDT P-value=0.013, X²=6.119, OR=1.95 in the UK sa...... TDT P-value=0.013, X²=6.119, OR=1.95 in the UK sample; TDT P-value=0.335, X²=0.931, OR=0.81 in the Turkish sample; TDT P-value=0.063, X²=3.47, OR=1.16 in the combined analysis More...	when considered alone, data from the UK sample but not the Turkish sample supported association and linkage between the SLC6A3 locus and ADHD, and in the combined analysis, they find only a marginal change in overall significance	Significant

Genes reported by this study (count: 1)