Parent-child DRD4 genotype as a potential biomarker for oppositional, anxiety, and repetitive behaviors in children with autism spectrum disorder.
The primary objective of the present study was to examine whether a combination of parent-child DRD4 genotypes results in more informative biomarkers of oppositional, separation anxiety, and repetitive behaviors in children with autism spectrum disorder (ASD). Based on prior research indicating the 7-repeat allele as a potential risk variant, participants were sorted into one of four combinations of parent-child genotypes. Owing to the possibility of parent-of-origin effects, analyses were conducted separately for mother-child (MC) and father-child (FC) dyads. Mothers completed a validated DSM-IV-referenced rating scale. Partial eta-squared (ηp(2)) was used to determine the magnitude of group differences: 0.01-0.06=small, 0.06-0.14=moderate, and >0.14=large. Analyses indicated that children in MC dyads with matched genotypes had the least (7-/7-) and most (7+/7+) severe mother-rated oppositional-defiant (ηp(2)=0.11) and separation anxiety (ηp(2)=0.19) symptoms. Conversely, youths in FC dyads with matched genotypes had the least (7-/7-) and most (7+/7+) severe obsessive-compulsive behaviors (ηp(2)=0.19) and tics (ηp(2)=0.18). Youths whose parents were both noncarriers had less severe tics than peers with at least one parental carrier, and the effect size was large (ηp(2)=0.16). There was little evidence that noncarrier children were rated more severely by mothers who were carriers versus noncarriers. Transmission Disequilibrium Test analyses provided preliminary evidence for undertransmission of the 2-repeat allele in youths with more severe tics (p=0.02). Parent genotype may be helpful in constructing prognostic biomarkers for behavioral disturbances in ASD; however, findings are tentative pending replication with larger, independent samples.
Gadow
Kenneth D
KD
Department of Psychiatry, Division of Child and Adolescent Psychiatry, Cody Center for Autism and Developmental Disabilities (Pediatrics), Putnam Hall, South Campus, Stony Brook University, Stony Brook, NY 11794-8790, USA. kenneth.gadow@stonybrook.edu
DeVincent
Carla J
CJ
Pisarevskaya
Victoria
V
Olvet
Doreen M
DM
Xu
Wenjie
W
Mendell
Nancy R
NR
Finch
Stephen J
SJ
Hatchwell
Eli
E
D000293:Adolescent; D000704:Analysis of Variance; D001008:Anxiety Disorders / Q000209:etiology / Q000235:genetics*; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000209:etiology / Q000235:genetics*; D015415:Biomarkers; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000150:complications / Q000235:genetics*; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000209:etiology / Q000235:genetics; D010287:Parent-Child Relations; D010290:Parents; D011569:Psychiatric Status Rating Scales; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D013981:Tic Disorders / Q000209:etiology / Q000235:genetics
D015415:Biomarkers; C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4