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

Association of ADHD with genetic variants in the 5'-region of the dopamine transporter gene: evidence for allelic heterogeneity
Association of ADHD with genetic variants in the 5'-region of the dopamine transporter gene: evidence for allelic heterogeneity
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.
attention deficit hyperactivity disorder (adhd), dopamine transporter gene (dat1), association study
1552-4841
Brookes, K.J.
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Xu, X.
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Anney, R.
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Franke, B.
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Zhou, K.
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Chen, Wai
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Banaschewski, T.
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Buitelaar, J.
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Ebstein, R.
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Eisenberg, J.
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Gill, M.
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Miranda, A.
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Oades, R.D.
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Roeyers, H.
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Rothenberger, A.
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Sergeant, J.
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Sonuga-Barke, E.
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Steinhausen, H.-C.
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Taylor, E.
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Faraone, S.V.
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Asherson, P.
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Brookes, K.J.
b18abfd0-f994-4d3c-923c-de551c2c705b
Xu, X.
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Anney, R.
d7b97910-6012-49e4-adc8-bce228fcab7f
Franke, B.
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Zhou, K.
b7f35885-4647-46b1-acf8-c3bae7f50755
Chen, Wai
ad64ca20-e814-4c31-a0ce-230287a988d4
Banaschewski, T.
ca2651e5-143a-4171-b6d0-3e3853b684d8
Buitelaar, J.
fa22aba5-1307-4627-9ae8-e564013a5af8
Ebstein, R.
451c2126-5196-41ff-81f9-490a200398e9
Eisenberg, J.
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Gill, M.
ae2696a2-c4b5-4a68-8f42-f26dbed5e251
Miranda, A.
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Oades, R.D.
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Roeyers, H.
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Rothenberger, A.
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Sergeant, J.
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Sonuga-Barke, E.
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Steinhausen, H.-C.
f93a201f-c58f-4b6b-b6fb-3ef730edfc05
Taylor, E.
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Faraone, S.V.
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Asherson, P.
4ecfa0c9-ea9c-47b9-aae8-429822c6c7ee

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).

Record type: Article

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.

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More information

Published date: 30 July 2008
Keywords: attention deficit hyperactivity disorder (adhd), dopamine transporter gene (dat1), association study

Identifiers

Local EPrints ID: 63808
URI: https://eprints.soton.ac.uk/id/eprint/63808
ISSN: 1552-4841
PURE UUID: 3fa51daf-1dd0-4298-8137-6a32521f9899

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Date deposited: 05 Nov 2008
Last modified: 13 Mar 2019 20:23

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Contributors

Author: K.J. Brookes
Author: X. Xu
Author: R. Anney
Author: B. Franke
Author: K. Zhou
Author: Wai Chen
Author: T. Banaschewski
Author: J. Buitelaar
Author: R. Ebstein
Author: J. Eisenberg
Author: M. Gill
Author: A. Miranda
Author: R.D. Oades
Author: H. Roeyers
Author: A. Rothenberger
Author: J. Sergeant
Author: E. Sonuga-Barke
Author: H.-C. Steinhausen
Author: E. Taylor
Author: S.V. Faraone
Author: P. Asherson

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