Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype in persistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD.
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.
Franke
Barbara
B
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. b.franke@antrg.umcn.nl
Vasquez
Alejandro Arias
AA
Johansson
Stefan
S
Hoogman
Martine
M
Romanos
Jasmin
J
Boreatti-Hümmer
Andrea
A
Heine
Monika
M
Jacob
Christian P
CP
Lesch
Klaus-Peter
KP
Casas
Miguel
M
Ribasés
Marta
M
Bosch
Rosa
R
Sánchez-Mora
Cristina
C
Gómez-Barros
Núria
N
Fernàndez-Castillo
Noèlia
N
Bayés
Mònica
M
Halmøy
Anne
A
Halleland
Helene
H
Landaas
Elisabeth T
ET
Fasmer
Ole B
OB
Knappskog
Per M
PM
Heister
Angelien J G A M
AJ
Kiemeney
Lambertus A
LA
Kooij
J J Sandra
JJ
Boonstra
A Marije
AM
Kan
Cees C
CC
Asherson
Philip
P
Faraone
Stephen V
SV
Buitelaar
Jan K
JK
Haavik
Jan
J
Cormand
Bru
B
Ramos-Quiroga
Josep Antoni
JA
Reif
Andreas
A
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
D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human