title: Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype in persistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD.
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.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. b.franke@antrg.umcn.nl
authors.forename: Barbara
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authors.lastname: Franke
authors.forename: Alejandro Arias
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authors.lastname: Vasquez
authors.forename: Stefan
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authors.lastname: Johansson
authors.forename: Martine
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authors.lastname: Hoogman
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authors.forename: Klaus-Peter
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authors.lastname: Lesch
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authors.lastname: Casas
authors.forename: Marta
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authors.lastname: Ribasés
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authors.lastname: Bosch
authors.forename: Cristina
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authors.lastname: Sánchez-Mora
authors.forename: Núria
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authors.lastname: Gómez-Barros
authors.forename: Noèlia
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authors.lastname: Fernàndez-Castillo
authors.forename: Mònica
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authors.lastname: Bayés
authors.forename: Anne
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authors.lastname: Halmøy
authors.forename: Helene
authors.initials: H
authors.lastname: Halleland
authors.forename: Elisabeth T
authors.initials: ET
authors.lastname: Landaas
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authors.initials: OB
authors.lastname: Fasmer
authors.forename: Per M
authors.initials: PM
authors.lastname: Knappskog
authors.forename: Angelien J G A M
authors.initials: AJ
authors.lastname: Heister
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authors.initials: LA
authors.lastname: Kiemeney
authors.forename: J J Sandra
authors.initials: JJ
authors.lastname: Kooij
authors.forename: A Marije
authors.initials: AM
authors.lastname: Boonstra
authors.forename: Cees C
authors.initials: CC
authors.lastname: Kan
authors.forename: Philip
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authors.lastname: Asherson
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Jan K
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authors.lastname: Buitelaar
authors.forename: Jan
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authors.lastname: Haavik
authors.forename: Bru
authors.initials: B
authors.lastname: Cormand
authors.forename: Josep Antoni
authors.initials: JA
authors.lastname: Ramos-Quiroga
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authors.lastname: Reif
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology; D002648:Child; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human