Multicenter Analysis of the SLC6A3/DAT1 VNTR Haplotype in Persistent ADHD Suggests Differential Involvement of the Gene in Childhood and Persistent ADHD
Open accessAbstract
Attention deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders with a worldwide prevalence around 4-5% in children and 1-4% in adults. Although ADHD is highly heritable and familial risk may contribute most strongly to the persistent form of the disorder, there are few studies on the genetics of ADHD in adults. In this paper, we present the first results of the International Multicentre Persistent ADHD Genetics CollaboraTion (IMpACT) that has been set up with the goal of performing research into the genetics of persistent ADHD. In this study, we carried out a combined analysis as well as a meta-analysis of the association of the SLC6A3/DAT1 gene with persistent ADHD in 1440 patients and 1769 controls from IMpACT and an earlier report. DAT1, encoding the dopamine transporter, is one of the most frequently studied genes in ADHD, though results have been inconsistent. A variable number tandem repeat polymorphism (VNTR) in the 3'-untranslated region (UTR) of the gene and, more recently, a haplotype of this VNTR with another VNTR in intron 8 have been the target of most studies. Although the 10/10 genotype of the 3'-UTR VNTR and the 10-6 haplotype of the two VNTRs are thought to be risk factors for ADHD in children, we found the 9/9 genotype and the 9-6 haplotype associated with persistent ADHD. In conclusion, a differential association of DAT1 with ADHD in children and in adults might help explain the inconsistencies observed in earlier association studies. However, the data might also imply that DAT1 has a modulatory rather than causative role in ADHD.
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In adults (and thus in persisting forms of the disorder), ADHD has been associated with the 9-repeat allele.
“For example, the DAT1 10-repeat allele is considered to increase risk for ADHD in children and adolescents, yet in adults (and thus, by definition, in persisting forms of the disorder) ADHD has been associated with the 9-repeat allele (Franke et al, 2008; Franke et al, 2010).”
From DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls (2010) · cites this paper as Franke et al, 2010
The DAT1 10-repeat allele is considered to increase risk for ADHD in children and adolescents.
“For example, the DAT1 10-repeat allele is considered to increase risk for ADHD in children and adolescents, yet in adults (and thus, by definition, in persisting forms of the disorder) ADHD has been associated with the 9-repeat allele (Franke et al, 2008; Franke et al, 2010).”
From DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls (2010) · cites this paper as Franke et al, 2010
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References 49 · Cited by 183
- Authors
- Franke, B., Vasquez, A. A., Johansson, S., Hoogman, M., Romanos, J., Boreatti-Hümmer, A., Heine, M., Jacob, C. P., Lesch, K.-P., Casas, M., Ribasés, M., Bosch, R., Sánchez-Mora, C., Gómez-Barros, N., Fernàndez-Castillo, N., Bayés, M., Halmøy, A., Halleland, H., Landaas, E. T., Fasmer, O. B., Knappskog, P. M., Heister, A. J. G. A. M., Kiemeney, L. A., Kooij, J. J. S., Boonstra, A. M., Kan, C. C., Asherson, P., Faraone, S. V., Buitelaar, J. K., Haavik, J., Cormand, B., Ramos-Quiroga, J. A., & Reif, A.
- Affiliations
- Radboud University Medical Center (NL)
- Haukeland University Hospital (NO)
- Radboud University Nijmegen (NL)
- University of Würzburg (DE)
- Universitat Autònoma de Barcelona (ES)
- Vall d'Hebron Hospital Universitari (ES)
- University of Bergen (NO)
- PsyQ (NL)
- King's College London (GB)
- SUNY Upstate Medical University (US)
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Franke, Barbara
- ORCID
- Franke, Barbara
- Johansson, Stefan
- Hoogman, Martine
- Jacob, Christian P
- Lesch, Klaus-Peter
- Casas, Miguel
- Ribasés, Marta
- Bosch, Rosa
- Halmøy, Anne
- Halleland, Helene
- Landaas, Elisabeth T
- Fasmer, Ole B
- Knappskog, Per M
- Kiemeney, Lambertus A
- Kooij, J J Sandra
- Asherson, Philip
- Faraone, Stephen V
- Buitelaar, Jan K
- Haavik, Jan
- Cormand, Bru
- Reif, Andreas
- Venue
- Neuropsychopharmacology
- Published
- 2009-11-04
- Volume
- 35
- Issue
- 3
- Pages
- 656-664
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3055604
- OpenAlex
- W2158689270
- Cited by
- 183
- References
- 49
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 12 · 2021: 5 · 2020: 7 · 2019: 10 · 2018: 14 · 2017: 12 · 2016: 10 · 2015: 23 · 2014: 15 · 2013: 14 · 2012: 23
- FWCI
- 9.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- VU Research Portal (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (acceptedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Fonds Psychische Gezondheid
- Norges Forskningsråd
- Hersenstichting
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- persistent ADHD, dopamine transporter, DAT1, 3' untranslated region polymorphism, genetic association, adult ADHD, childhood ADHD
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Attention Deficit Disorder with Hyperactivity, Child, Female, Haplotypes, Humans, Male, Middle Aged, Retrospective Studies, Minisatellite Repeats, Internationality, Dopamine Plasma Membrane Transport Proteins, Young Adult
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