Direct and Indirect Genetic Effects on Child ADHD Traits in Early and Mid-Childhood: Trio Genome-Wide Complex Trait Analyses in a Large Norwegian Birth Registry Cohort

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. 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. Differing patterns of direct and indirect genetic effects were observed in early and mid-childhood, with predominantly maternal indirect genetic effects on ADHD traits at age 5, and roughly equal direct genetic effects and maternal indirect effects on ADHD traits at age 8. However, large standard errors hindered confident inference as to the relative importance of specific effects, and model fit comparisons ultimately favored models with no indirect genetic effects at age 5 and 8, as well as no direct genetic effects at age 5. We do not find clear evidence of indirect genetic effects of maternal or paternal genotype on child ADHD traits at ages 5 and 8, nor direct genetic effects on child ADHD traits at age 5. While previous findings of indirect genetic effects on ADHD subdomains at ages 3 and 8 broadly support the plausibility of indirect genetic effects operating on total ADHD scores at ages 5 and 8, it appears that indirect genetic effects on overall ADHD trait magnitude may be more difficult to estimate with precision than subdomain-specific effects.