Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD.
Previous studies have found heterogeneous association between DAT1-3'-UTR-VNTR and attention deficit hyperactivity disorder (ADHD). Various proportions of conduct disorder (CD) comorbidity in their ADHD samples may partially explain the observational discrepancies. Evidence for this comes from family and twin studies which found ADHD probands with CD (ADHD + CD) are genetically different from those without CD (ADHD - CD). Genotypes of 20 DAT1 markers were analyzed in 576 trios, consisting of 141 ADHD + CD and 435 ADHD - CD. In addition to the classical TDT test, a specific genetic heterogeneity test was performed to identify variants that have different transmission patterns in the two phenotypic subgroups. After multiple-test correction, rs40184 and rs2652511 were significant in TDT tests. Further heterogeneity test found the two SNPs had a significant transmission pattern difference between ADHD + CD and ADHD - CD children, indicating that DAT1 has a significantly greater genetic influence on ADHD without CD. Although the result needs further replications, it does highlight the importance of selecting genetically homogeneous samples for molecular genetic analyses of ADHD.
MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, London, United Kingdom.
Kaixin
K
Zhou
Wai
W
Chen
Jan
J
Buitelaar
Tobias
T
Banaschewski
Robert D
RD
Oades
Barbara
B
Franke
Edmund
E
Sonuga-Barke
Richard
R
Ebstein
Jacques
J
Eisenberg
Michael
M
Gill
Iris
I
Manor
Ana
A
Miranda
Fernando
F
Mulas
Herbert
H
Roeyers
Aribert
A
Rothenberger
Joseph
J
Sergeant
Hans-Christoph
HC
Steinhausen
Jessica
J
Lasky-Su
Eric
E
Taylor
Keeley J
KJ
Brookes
Xiaohui
X
Xu
Benjamin M
BM
Neale
Fruhling
F
Rijsdijk
Margaret
M
Thompson
Philip
P
Asherson
Stephen V
SV
Faraone
D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics*; D016009:Chi-Square Distribution; D002648:Child; D015897:Comorbidity; D019955:Conduct Disorder / Q000453:epidemiology / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide
D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; C493214:SLC6A3 protein, human