Mapping relationships between ADHD genetic liability, stressful life events, and ADHD symptoms in healthy adults

Attention-deficit/hyperactivity disorder (ADHD) symptoms are continuously distributed in the general population, where both genetic and environmental factors play roles. Stressful life events (SLEs) have been associated with ADHD diagnosis, but the relationship between ADHD genetic liability, SLEs, and ADHD symptoms in healthy individuals is less clear. Using a sample of 1,531 healthy adults (average age 26.9 years; 55.8% female), we investigated relationships between ADHD polygenic risk scores (ADHD-PRSs), SLEs, and ADHD symptoms in a general population sample. Confirming earlier findings in an overlapping sample, all SLE-measures assessed (lifetime SLEs, recent SLEs, and childhood trauma (CT)) were significantly correlated with total ADHD, inattention (IA), and hyperactivity-impulsivity (HI) scores (r² range = .08-.15; all p < .005). ADHD-PRSs was associated with HI (R²_best-fit  = .37%), lifetime SLEs (R²_best-fit  = .56%), and CT (R²_best-fit  = .40%). Mediation analyses showed that lifetime SLEs partially mediated the association between ADHD-PRSs and HI (indirect effect: β = 68.6, bias corrected accelerated 95% confident interval (BCa95%CI) [11.9, 131.0], p = .016, proportion mediated (P_M ) =19.5%), with strongest effects contributed by CT (β = 34.4, BCa95%CI [0.4, 76.5], p = .040, P_M  = 9.8%). On the other hand, HI partially mediated the association between the ADHD-PRSs and lifetime SLEs (β = 42.9, BCa95%CI [7.3, 83.9], p = .014, P_M  = 18.8%). Our study observed a complex relationship of genetic and environmental risk factors contributing to ADHD symptoms in the healthy adult population.