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.
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Acknowledgements
We are grateful to all patients and controls for their participation in the study. We thank Pål Borge and Sigrid Erdal for help with genotyping of the Norwegian samples. We thank Mariana Nogueira and Montse Corrales for their involvement in the clinical assessment and Lucas Brunso for his contribution to the genotyping in Spain. We thank Remco Makkinje and Marlies Naber for help with genotyping in The Netherlands. The Dutch controls were derived from the Nijmegen Biomedical Study. Principal investigators of the Nijmegen Biomedical Study are LALM Kiemeney, M den Heijer, ALM Verbeek, DW Swinkels, and B Franke. We thank Dr Marcella Rietschel, Dr Esther Sobanski, and Dr Josef Frank for providing us with the DAT1 genotype information from their study. The Norwegian part of the study was sponsored by Research Council of Norway. Financial support for the Spanish part of the study was received from ‘Instituto de Salud Carlos III-FIS, Spain’ (PI040524, PI041267) and ‘Agència de Gestió d’Ajuts Universitaris i de Recerca-AGAUR’ (2005SGR00848). MB and MR are recipients of a ‘Ramon y Cajal’ and a ‘Juan de la Cierva’ contract, respectively, from ‘Ministerio de Ciencia y Tecnología’ (Spain). The Dutch part of the project was supported by the Hersenstichting Nederland (Fonds Psychische Gezondheid).
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Franke, B., Vasquez, A., Johansson, S. et al. Multicenter Analysis of the SLC6A3/DAT1 VNTR Haplotype in Persistent ADHD Suggests Differential Involvement of the Gene in Childhood and Persistent ADHD. Neuropsychopharmacol 35, 656–664 (2010). https://doi.org/10.1038/npp.2009.170
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DOI: https://doi.org/10.1038/npp.2009.170
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