Direct and indirect genetic effects on child ADHD traits: Trio genome-wide complex trait analyses in a large Norwegian birth registry cohort

Background: Genetic variants in family members may exert environmentally mediated indirect genetic effects on children’s attention-deficit hyperactivity disorder (ADHD) traits. We set out to quantify the indirect genetic effects of parents’ genotypes on children’s ADHD traits as measured in early and mid-childhood. Methods: We analyzed data from genotyped trios of children, mothers, and fathers of European ancestry from the Norwegian Mother, Father and Child Cohort Study (MoBa) birth cohort. Child ADHD data were available for analytic subsamples of 12,374 trios at age 5 (children 50.5% male), and 12,714 trios at age 8 (children 50.9% male). We quantified direct genetic effects of children’s genotype and indirect effects of mothers’ and fathers’ genotypes on children’s ADHD traits at each age. Results: At age 5, maternal indirect genetic effects explained roughly twice as much variance in children’s ADHD traits as did child direct genetic effects. At age 8, maternal indirect genetic effects and child direct genetic effects explained roughly equal portions of variance in child ADHD traits. However, issues with power were evident throughout analyses and precluded confident interpretation of indirect genetic effects. Conclusions: We find tentative evidence for heritable parental traits exerting environmental effects on child ADHD traits in early and mid-childhood, suggesting that maternal genotypes exert indirect effects on children’s traits after accounting for the direct effects of children’s own genotype. However, future studies with larger samples are needed to enable clear inferences on the importance of indirect genetic effects for children’s ADHD traits.