Impact of autism-associated genetic variants in interaction with environmental factors on ADHD comorbidities: an exploratory pilot study

Attention-deficit/hyperactivity disorder (ADHD) is determined by genetic and environmental factors, and shares genetic risk with ASD. Functional single-nucleotide polymorphisms of the metabotropic glutamatergic signaling pathway are reported to increase the risk for ASD. The aim of this pilot study was to explore the main effects of respective ASD variants as well as their interaction effects with well-replicated ADHD environmental risk factors on the risk for ADHD, ADHD symptom severities, and comorbidities. We included 318 children with ADHD, aged 5–13 years, and their parents ( N = 164 trios, N = 113 duos, N = 41 singletons). Interaction of ASD risk variants CYFIP1 -rs7170637, CYFIP1 -rs3693, CAMK4 -rs25925, and GRM1 -rs6923492 with prenatal biological and lifetime psychosocial risk factors was explored in a subsample with complete environmental risk factors ( N = 139 trios, N = 83 duos, two singletons) by transmission disequilibrium test and stepwise regression analyses. We identified nominally significant (alpha