Association of ADHD with genetic variants in the 5'-region of the dopamine transporter gene: evidence for allelic heterogeneity


Brookes, K.J., Xu, X., Anney, R., Franke, B., Zhou, K., Chen, Wai, Banaschewski, T., Buitelaar, J., Ebstein, R., Eisenberg, J., Gill, M., Miranda, A., Oades, R.D., Roeyers, H., Rothenberger, A., Sergeant, J., Sonuga-Barke, E., Steinhausen, H.-C., Taylor, E., Faraone, S.V. and Asherson, P. (2008) Association of ADHD with genetic variants in the 5'-region of the dopamine transporter gene: evidence for allelic heterogeneity. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics (doi:10.1002/ajmg.b.30782).

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Original Publication URL: http://dx.doi.org/10.1002/ajmg.b.30782

Description/Abstract

Multiple studies have reported an association between attention deficit hyperactivity disorder (ADHD) and the 10-repeat allele of a variable number tandem repeat (VNTR) polymorphism in the 3-untranslated region (3UTR) of the dopamine transporter gene (DAT1). Yet, recent meta-analyses of available data find little or no evidence for this association; although there is strong evidence for heterogeneity between datasets. This pattern of findings could arise for several reasons including the presence of relatively rare risk alleles on common haplotype backgrounds or the functional interaction of two or more loci within the gene. We previously described the importance of a specific haplotype at the 3 end of DAT1, as well as the identification of associated single nucleotide polymorphisms (SNPs) within or close to 5 regulatory sequences. In this study we replicate the association of SNPs at the 5 end of the gene and identify a specific risk haplotype spanning the 5 and 3 markers. These findings indicate the presence of at least two loci associated with ADHD within the DAT1 gene and suggest that either additive or interaction effects of these two loci on the risk for ADHD. Overall these data provide further evidence that genetic variants of the dopamine transporter gene confer an increased risk for ADHD.

Item Type: Article
ISSNs: 1552-4841 (print)
Related URLs:
Keywords: attention deficit hyperactivity disorder (adhd), dopamine transporter gene (dat1), association study
Subjects: Q Science > QH Natural history > QH426 Genetics
B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RJ Pediatrics > RJ101 Child Health. Child health services
Divisions: University Structure - Pre August 2011 > School of Psychology > Division of Clinical Neuroscience
ePrint ID: 63808
Date Deposited: 05 Nov 2008
Last Modified: 27 Mar 2014 18:45
URI: http://eprints.soton.ac.uk/id/eprint/63808

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