Cognitive functioning in affected sibling pairs with ADHD: familial clustering and dopamine genes.
BACKGROUND
This paper examines familiality and candidate gene associations of cognitive measures as potential endophenotypes in attention-deficit/hyperactivity disorder (ADHD).


METHODS
The sample consists of 540 participants, aged 6 to 18, who were diagnosed with ADHD from 251 families recruited for a larger genetic study of ADHD. All members of the family underwent psychiatric interviews and children were administered a large battery of cognitive tasks. Subjects were genotyped for several dopaminergic candidate genes (DAT1, DRD4, and DRD5).


RESULTS
Performance on measures of intelligence, working memory, and set-shifting had the highest sibling correlations and exhibited significant familial clustering. The 7-repeat allele of the dopamine receptor D4 (DRD4) gene was associated with poor performance on measures of intelligence, color naming, interference control, and working memory. There were no significant associations with DAT1 and DRD5.


CONCLUSIONS
Sibling correlations, familial clustering and candidate gene associations provide strong support for verbal working memory as a candidate endophenotype for ADHD. More complex models of, and larger sample sizes for, genetic association with cognitive functions are encouraged for future study.
Loo
Sandra K
SK
UCLA Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA, USA. sloo@mednet.ucla.edu
Rich
Erika Carpenter
EC
Ishii
Janeen
J
McGough
James
J
McCracken
James
J
Nelson
Stanley
S
Smalley
Susan L
SL
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D002648:Child; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology*; D004298:Dopamine / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010641:Phenotype; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics; D050641:Receptors, Dopamine D5 / Q000235:genetics; D012801:Sibling Relations
C493599:DRD4 protein, human; C493605:DRD5 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D004298:Dopamine