background Symptoms of autism spectrum disorder (asd) and attention deficit hyperactivity disorder (adhd) often co-occur. Given the previously found familiality of asd symptoms in children with adhd, addressing these symptoms may be useful for genetic association studies, especially for candidate gene findings that have not been consistently replicated for adhd.
aim To study gene-environment interaction (GxE) in explaining comorbid asd symptoms in patients with adhd.
method We studied the association of the catechol o-methyltransferase (comt) Val-158Met polymorphism and the serotonin transporter (slc6a4/sert/5-htt) 5-httlpr insertion/deletion polymorphism with asd symptoms in children with adhd, and whether these polymorphisms would interact with pre- and perinatal risk factors, i.e., maternal smoking during pregnancy and low birth weight. Analyses were performed using linear regression in 207 Dutch participants with combined type adhd of the International Multicenter adhd Genetics (image) study, and repeated in an independent adhd sample (n = 439) selected from the TRacking Adolescents’ Individual Lives Survey (trails). Dependent variables were the total and subscale scores of the Children’s Social Behavior Questionnaire (csbq).
results No significant main effects of comt Val158Met, 5-httlpr, maternal smoking during pregnancy and low birth weight on asd symptoms were found. However, the comt Val/Val genotype interacted with maternal smoking during pregnancy in increasing stereotyped behavior in the image sample (p = 0.008); this interaction reached significance in the trails sample after correction for confounders (p = 0.02). In the image sample, the 5-httlpr S/S genotype interacted with maternal smoking during pregnancy, increasing problems in social interaction (p = 0.02), and also interacted with low birth weight, increasing rigid behavior (p = 0.03). Findings for 5-httlpr in the trails sample were similar, albeit for related csbq subscales.
conclusion These findings suggest gene-environment interaction effects on asd symptoms in children with adhd.