Susceptibility genes for a trait measure of attention deficit hyperactivity disorder: a pilot study in a non-clinical sample of twins.
Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder, and molecular genetic studies are underway, with most researchers focusing on identifying susceptibility genes in clinical samples with ADHD. An alternative approach is to search for quantitative trait loci underlying the trait measure of ADHD in non-clinical samples. Positive findings of association of the dopamine transporter DAT1 480 bp allele (allele 10) and the DRD4 7 repeat allele with clinical ADHD have been previously reported. In this pilot study, we examined these polymorphisms in a selected population-based sample of twins (50 high scoring pairs, 42 low scoring pairs). There was a trend for an increase in the frequency of the dopamine receptor DRD4 7 repeat allele in the high-scoring concordant monozygotic twins (odds ratio=1.4). Although this result was not statistically significant, the frequency of the 7 repeat allele was similar to that reported for our clinic sample of ADHD patients drawn from the same geographical area. There was a non-significant trend for an increased frequency of the DAT1 allele 10 (odds ratio=1.3). These results suggest that a molecular genetic study based on a questionnaire-derived measure of ADHD in a non-clinical sample is feasible and the results appear to be comparable with those from studies of clinical cases. However, sample size and power are key issues to consider when using this approach.
Payton
A
A
ARC Epidemiology Unit and Department of Child and Adolescent Psychiatry, University of Manchester, Manchester, UK.
Holmes
J
J
Barrett
J H
JH
Sham
P
P
Harrington
R
R
McGuffin
P
P
Owen
M
M
Ollier
W
W
Worthington
J
J
Thapar
A
A
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010865:Pilot Projects; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D029701:Saccharomyces cerevisiae Proteins; D011795:Surveys and Questionnaires; D014430:Twins, Monozygotic / Q000235:genetics* / Q000523:psychology
D002352:Carrier Proteins; C060858:DAT1 protein, S cerevisiae; D004268:DNA-Binding Proteins; C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D029701:Saccharomyces cerevisiae Proteins; D050638:Receptors, Dopamine D4