1. ¹Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
2. ²Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
3. ³Department of Biomedicine, University of Bergen, Bergen, Norway
4. ⁴Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
5. ⁵Department of Psychiatry and Psychotherapy, Clinical and Molecular Psychobiology, University of Würzburg, Würzburg, Germany
6. ⁶Interdiciplinary Center for Clinical Research (IZKF), University of Würzburg, Würzburg, Germany
7. ⁷Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
8. ⁸Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain
9. ⁹Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Catalonia, Spain
10. ¹⁰Genes and Disease Program, Center for Genomic Regulation (CRG), UPF, Barcelona, Catalonia, Spain
11. ¹¹CIBER Epidemiología y Salud Pública, Instituto de Salud Carlos III (CRG), Barcelona, Catalonia, Spain
12. ¹²Centro Nacional de Genotipado (CeGen), Barcelona, Catalonia, Spain
13. ¹³Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway
14. ¹⁴Department of Psychiatry, Haukeland University Hospital, Bergen, Norway
15. ¹⁵Department of Clinical Medicine, University of Bergen, Bergen, Norway
16. ¹⁶Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
17. ¹⁷PsyQ, Psycho-Medical Programs, Program Adult ADHD, The Hague, The Netherlands
18. ¹⁸MRC Social Genetic and Developmental Psychiatry, Institute of Psychiatry, Kings College London, London, UK
19. ¹⁹Departments of Psychiatry and Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York, USA
20. ²⁰CIBER Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Catalonia, Spain
21. ²¹Institut de Biomedicina de la Universitat de Barcelona (IBUB), Catalonia, Spain

Correspondence: Dr B Franke, Department of Human Genetics (855), Radboud University, Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. Tel: +310 243 610 181; Fax: +310 243 616 658; E-mail: b.franke@antrg.umcn.nl

²²Participating as representative of the Nijmegen Biomedical Study.

²³These authors contributed equally to this work.

Received 3 April 2009; Revised 5 August 2009; Accepted 13 August 2009; Published online 4 November 2009.

Abstract

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.