Exposomic and polygenic contributions to allostatic load in early adolescence

Abstract

Allostatic load (AL) is the cumulative ‘wear and tear’ on the body due to chronic adversity. We tested the poly-environmental (exposomic) and polygenic contributions to AL and their combined contribution to adolescent mental health. In this cohort study of N = 5,036 diverse youth (mean age 12 years) from the Adolescent Brain Cognitive Development Study, we calculated a latent AL score, childhood exposomic risk and genetic risk. We tested the associations of exposomic and polygenic risks with AL using linear mixed-effects models, and tested the mediating role of AL on the pathway from exposomic/polygenic risk to mental health. AL was significantly lower among non-Hispanic white youth compared to Hispanic and non-Hispanic black youth. Childhood exposomic burden was associated with AL in adolescence (β = 0.25, 95% CI 0.22–0.29, P < 0.001). In subset analysis of participants of European-like genetic ancestry (n = 2,928), the type 2 diabetes polygenic risk score (T2D-PRS; β = 0.11, 95% CI 0.07–0.14, P < 0.001) and major depressive disorder (MDD)-PRS (β = 0.05, 95% CI 0.02–0.09, P = 0.003) were associated with AL. Both PRSs showed significant gene–environment interactions such that, with greater polygenic risk, associations between exposome and AL were stronger. AL significantly mediated the indirect path from exposomic risk at age 11 years, and from both MDD-PRS and T2D-PRS to psychopathology at age 12 years. Our findings show that AL can be quantified in youth and is associated with exposomic and polygenic burden, supporting the diathesis–stress model. Using a large US cohort of adolescents, the authors examine exposomic and polygenic contributions to allostatic load and a mediating role of allostatic load on the path from exposomic and polygenic risks to psychopathology.