Intelligence in DSM-IV combined type attention-deficit/hyperactivity disorder is not predicted by either dopamine receptor/transporter genes or other previously identified risk alleles for attention-deficit/hyperactivity disorder.
A major goal of genetic studies of attention deficit hyperactivity disorder (ADHD) is to identify individual characteristics that might help segregate the disorder's inherent heterogeneity. [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] recently reported a potentially important association between two dopamine-related risk polymorphisms (DRD4 variable number tandem repeat (VNTR) in exon 3 and DAT1 VNTR in the 3' UTR) and lowered IQ in ADHD. The objective of the current study was to replicate the [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] findings in a clinical sample and to extend the analysis to a large range of alternative SNP markers of putative ADHD risk alleles identified in a recent study [Brookes et al. (2006); Mol Genet 11:934-953]. Participants were 1081 children and adolescents with a research-confirmed combined type ADHD diagnosis and 1300 unaffected siblings who took part in the International Multi-centre ADHD Genetics (IMAGE) project. They were recruited from multiple settings from across Europe: Belgium, Britain, Germany, Ireland, Israel, Netherlands, Spain and Switzerland. The results were that ADHD was associated with reduced IQ. However, there was no association between the two dopamine-related risk polymorphisms and IQ in either the probands or their siblings. Furthermore, other selected genetic markers previously demonstrated to be associated with ADHD in this sample were not associated with IQ. This large scale study with a clinically ascertained and regorously diagnosed sample failed to replicate the association between genetic polymorphisms in the dopamine system and IQ in ADHD. We also observed no association of other SNPs with IQ in ADHD.
Sonuga-Barke
Edmund J S
EJ
School of Psychology, University of Southampton, Southampton, UK. ejb3@soton.ac.uk
Brookes
Keeley-Joanne
KJ
Buitelaar
Jan
J
Anney
Richard
R
Bitsakou
Paraskevi
P
Baeyens
Dieter
D
Buschgens
Cathelijne
C
Chen
Wai
W
Christiansen
Hanna
H
Eisenberg
Jacques
J
Kuntsi
Jonna
J
Manor
Iris
I
Meliá
Amanda
A
Mulligan
Aisling
A
Rommelse
Nanda
N
Müller
Ueli C
UC
Uebel
Henrik
H
Banaschewski
Tobias
T
Ebstein
Richard
R
Franke
Barbara
B
Gill
Michael
M
Miranda
Ana
A
Oades
Robert D
RD
Roeyers
Herbert
H
Rothenberger
Aribert
A
Sergeant
Joseph
J
Steinhausen
Hans Christoph
HC
Thompson
Margaret
M
Taylor
Eric
E
Asherson
Philip
P
Faraone
Stephen V
SV
D000293:Adolescent; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics / Q000523:psychology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007360:Intelligence; D008297:Male; D011954:Receptors, Dopamine / Q000235:genetics*; D012307:Risk Factors
D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine