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 (ηp2) 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 (ηp2 = 0.11) and separation anxiety (ηp2 = 0.19) symptoms. Conversely, youths in FC dyads with matched genotypes had the least (7−/7−) and most (7+/7+) severe obsessive-compulsive behaviors (ηp2 = 0.19) and tics (ηp2 = 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 (ηp2 = 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.