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	Gill M, 19979246671
Citation	Gill M., Daly G., Heron S., Hawi Z. and Fitzgerald M. (1997) "Confirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism." Mol Psychiatry, 2(4): 311-3.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	26 trios and 14 parent/proband pairs
Predominant Ethnicity	Caucasian
Population	Ireland
Age Group	Children/Adolescents

Detail Info

Summary	Attention deficit hyperactivity disorder (ADHD) is a common condition of childhood the symptoms of which include inattention, excessive motor activity, inpulsivity and distractibility. It is strongly familial and twin and adoption studies suggest that the familiality is due, at least in part, to shared genes. Gillis et al found concordance rates in ADHD for MZ and DZ twins of 81% and 29% respectively. Stimulant drugs (eg, methylphenidate) are effective in the treatment of ADHD and inhibit the dopamine transporter. This has led to the development of a hypodopaminergic hypothesis for the disease. Cook et al examined a 3' variable number of tandem repeat (VNTR) polymorphism at the dopamine transporter gene (DAT1) in a sample of 49 ADHD patients and their parents, using the haplotype relative risk (HRR) method. They found a significant association (X² = 7.29, 1 d.f., P=0.007) between ADHD and the 480-bp DAT1 VNTR allele. The authors stressed the importance of independent replication and have achieved this in a study of 40 probands and their parents, using the same robust HRR method. As in the study of Cook et al they found that the 480-bp allele was preferentially transmitted to ADHD probands (X² = 6.07, 1 d.f., P=0.014).
Total Sample	Forty probands and 68 parents were genotyped. Information on transmission of alleles was obtained from 26 trios and 14 parent/proband pairs. Four of the proband/parent pairs were doubly heterozygous and thus uninformative.
Sample Collection	A series of children, suffering from ADHD according to their clinicians were recruited from child psychiatric clinics in West County Dublin and from the Hyperactive Children's Support Group of Ireland.
Diagnosis Description	The clinical assessment included: (1) the Child Behaviour Checklist, a check list designed to obtain reports of children's behavioural problems and social competencies from their parents; (2) the Connors Parent Rating Scale which has been found particularly useful in the identification of hyperkinetic children; (3) the Comprehensive Teachers Rating Scale, which is completed by teachers and rates the four principle factors of ADHD behaviour; and (4) the Hyperactive and Attention Evaluation of the University of Chicago which is an instrument, administered to parents, focusing on semi-structured DSM-IIIR diagnostic criteria for ADHD. A consensus diagnosis, based on all available clinical data and the rating scales as above was reached between the child psychiatrist (MF) and the psychologist (GD).
Technique	DNA was extracted from buccal cells using a cytology brush. PCR amplification of the region flanking the DAT1 40-bp VNTR was achieved using the following pair of primers: Sense (5' TGT GGT GTA GGG AAC GGC CTG AG 3'), antisense (5' CTT CCT GGA GGT CAC GGC TCA AGG 3').
Analysis Method	Genotypes were assigned for each child and for all available parents. By reference to the proband's genotype, each parental allele was scored as to whether it was transmitted or not transmitted. Given the null hypothesis of linkage equilibrium, the probability that a parental allele will be transmitted to the proband is 0.50. In a sample of probands and parents, if the frequency of transmission of an allele deviates from 50% on the basis of a X² test, evidence for an association exists. This is known as the haplotype relative risk.
Result Description	Two alleles were detected in the parental sample: a 480-bp allele with a frequency of 0.71 and a 440-bp allele with a frequency of 0.29. HRR analysis revealed a significant association between ADHD and the 480-bp DAT1 allele as strong an association as was found by Cook et al. Of note, in the six trios where both father and mother are heterozygous 480/440, in three cases the proband is homozygous for the 480-bp allele and in the remaining three cases the offspring is heterozygous 440/480. None of the six probands was homozygous for the 440-bp allele.

Other variant reported by this study (count: 1)

Genes reported by this study (count: 1)