TY - JOUR
T1 - Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype in persistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD
AU - Franke, Barbara
AU - Vasquez, Alejandro Arias
AU - Johansson, Stefan
AU - Hoogman, Martine
AU - Romanos, Jasmin
AU - Boreatti-Hümmer, Andrea
AU - Heine, Monika
AU - Jacob, Christian P.
AU - Lesch, Klaus Peter
AU - Casas, Miguel
AU - Ribasés, Marta
AU - Bosch, Rosa
AU - Sánchez-Mora, Cristina
AU - Gómez-Barros, Nria
AU - Fernndez-Castillo, Noèlia
AU - Bayés, Mònica
AU - Halmøy, Anne
AU - Halleland, Helene
AU - Landaas, Elisabeth T.
AU - Fasmer, Ole B.
AU - Knappskog, Per M.
AU - Heister, Angelien J.G.A.M.
AU - Kiemeney, Lambertus A.
AU - Kooij, J. J.Sandra
AU - Boonstra, A. Marije
AU - Kan, Cees C.
AU - Asherson, Philip
AU - Faraone, Stephen V.
AU - Buitelaar, Jan K.
AU - Haavik, Jan
AU - Cormand, Bru
AU - Ramos-Quiroga, Josep Antoni
AU - Reif, Andreas
PY - 2010/2/1
Y1 - 2010/2/1
N2 - 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. © 2010 Nature Publishing Group All rights reserved.
AB - 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. © 2010 Nature Publishing Group All rights reserved.
KW - Dopamine
KW - Neurogenetics
KW - Psychiatry and behavioral sciences
KW - Transporters
U2 - 10.1038/npp.2009.170
DO - 10.1038/npp.2009.170
M3 - Article
SN - 0893-133X
VL - 35
SP - 656
EP - 664
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 3
ER -