Association of the dopamine transporter (DAT1) 10/10-repeat genotype with ADHD symptoms and response inhibition in a general population sample

被引:161
作者
Cornish, KM
Manly, T
Savage, R
Swanson, J
Morisano, D
Butler, N
Grant, C
Cross, G
Bentley, L
Hollis, CP
机构
[1] McGill Univ, Neurosci Lab Res & Educ Dev Disorders, Montreal, PQ, Canada
[2] McGill Univ, Fac Med, Dept Neurol & Neurosurg, Montreal, PQ, Canada
[3] Univ Nottingham, Div Psychiat, Nottingham NG7 2RD, England
[4] Addenbrookes Hosp, MRC, Cognit & Brain Sci Unit, Cambridge, England
[5] McGill Univ, Dept Educ Psychol, Montreal, PQ, Canada
[6] Univ Calif Irvine, UCI Child Dev Ctr, Irvine, CA USA
[7] Univ London, Inst Educ, Ctr Longitudinal Studies, London WC1N 1AZ, England
[8] City Hosp Nottingham, Dept Mol Genet, Nottingham, England
关键词
ADHD; DAT1; genetic association; cognition; QTL approach;
D O I
10.1038/sj.mp.4001641
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Association between attention-deficit hyperactivity disorder (ADHD) and the 10-repeat allele of the dopamine transporter gene (DAT1) has been reported in independent clinical samples using a categorical clinical definition of ADHD. The present study adopts a quantitative trait loci (QTL) approach to examine the association between DAT1 and a continuous measure of ADHD behaviours in a general-population sample, as well as to explore whether there is an independent association between DAT1 and performance on neuropsychological tests of attention, response inhibition, and working memory. From an epidemiological sample of 872 boys aged 6-11 years, we recruited 58 boys scoring above the 90th percentile for teacher reported ADHD symptoms (SWAN ADHD scale) and 68 boys scoring below 10th percentile for genotyping and neuropsychological testing. A significant association was found between the DAT1 homozygous 10/10-repeat genotype and high-scoring boys (chi(2)square=4.6, P < 0.03; odds ratio = 2.4, 95% CI 1.1-5.0). Using hierarchical linear regression, a significant independent association was found between the DAT1 10/10-repeat genotype and measures of selective attention and response inhibition after adjusting for age, IQ, and ADHD symptoms. There was no association between DAT1 and any component of working memory. Furthermore, performance on tasks of selective attention although associated with DAT1 was not associated with SWAN ADHD high scores after controlling for age and IQ. In contrast, impairment on tasks that tapped sustained attention and the central executive component of working memory were found in high-scoring boys after adjusting for age and IQ. The results suggest that DAT1 is a QTL for continuously distributed ADHD behaviours in the general population and the cognitive endophenotype of response inhibition.
引用
收藏
页码:686 / 698
页数:13
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