The relation of the dopamine transporter gene (DAT1) to symptoms of internalizing disorders in children.
The relation of the dopamine transporter gene (DAT1) to symptoms of internalizing disorders, Tourette's disorder, and obsessive-compulsive disorder was examined using both within- and between-family tests of association. The sample consisted of clinic-referred children and their siblings and controls and their siblings. Between-family association was examined via the association of DAT1 genotypes with disorder symptoms in the population. Symptoms of all eight disorders increased with a greater number of 10-repeat DAT1 alleles. Using a quantitative transmission disequilibrium test (QTDT), linkage and within-family association was indicated by increased symptoms in children who received 10 repeat alleles from heterozygous parents relative to children who received 9 repeat alleles. Four disorders were associated with DAT1 using the QTDT: generalized anxiety, social phobia, obsessive-compulsive, and Tourette's. The effects of comorbidity were investigated by repeating the same between- and within-family analyses on residual scores, with any effects of attention deficit hyperactivity disorder symptoms removed. Although the residuals were associated less strongly with DAT1 than were the original scores, three disorders continued to show association both between and within families: generalized anxiety, Tourette's, and social phobia.
University of Arizona, Tucson 85721, USA. dcr091@ag.arizona.edu
D C
DC
Rowe
C
C
Stever
J M
JM
Gard
H H
HH
Cleveland
M L
ML
Sanders
A
A
Abramowitz
S T
ST
Kozol
J H
JH
Mohr
S L
SL
Sherman
I D
ID
Waldman
D000293:Adolescent; D001008:Anxiety Disorders / Q000150:complications / Q000235:genetics*; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D050483:Dopamine Plasma Membrane Transport Proteins; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009679:Nuclear Family; D019655:Quantitative Trait, Heritable; D005879:Tourette Syndrome / Q000150:complications / Q000235:genetics*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human