SNPs in dopamine D2 receptor gene (DRD2) and norepinephrine transporter gene (NET) are associated with continuous performance task (CPT) phenotypes in ADHD children and their families.
Haplotype-tagging SNP analyses were conducted to identify molecular genetic substrates of quantitative phenotypes derived from performance on a Continuous Performance Task (CPT). Three hundred sixty-four individuals were sampled from 152 families ascertained on the basis of at least one child having ADHD. Probands, their affected and unaffected siblings, and parents were administered a CPT. Four different components of performance were analyzed and tested for association with SNPs from 10 candidate genes involved in monoaminergic function. After correcting for multiple comparisons and controlling for multiple individuals from the same family, significant associations were identified between commission errors and SNPs in the DRD2 gene (rs2075654, rs1079596), and between reaction time variability and a SNP in the NET gene (rs3785155). These findings suggest that commission errors and reaction time variability are excellent candidates as ADHD endophenotypes based on previously published criteria. Results also shed light on the molecular genetic basis of specific processes that may underlie the disorder.
Kollins
S H
SH
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina, USA . kolli001@mc.duke.edu
Anastopoulos
A D
AD
Lachiewicz
A M
AM
FitzGerald
D
D
Morrissey-Kane
E
E
Garrett
M E
ME
Keatts
S L
SL
Ashley-Koch
A E
AE
D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007407:Interviews as Topic; D008297:Male; D009483:Neuropsychological Tests; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D009679:Nuclear Family; D010290:Parents; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D035781:Siblings
D050484:Norepinephrine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; C493227:SLC6A2 protein, human