Polygenic risk for epigenetic aging and adverse life experiences interact to predict growth in adolescent depression in a racially/ethnically diverse sample.

Introduction: Research has yet to examine the interplay between indices of environmental risk and resilience processes and genetic predisposition for epigenetic aging in predicting early adolescent depressive symptoms. In the current study we examine whether adverse life events and parental acceptance moderate polygenic predisposition for GrimAge epigenetic aging in predicting trajectories of depressive symptoms across early adolescence. Method: Using data from the Adolescent Brain Development Study (ABCD, N = 11,875), we created polygenic scores for GrimAge, and examined whether exposure to adverse life events and parental acceptance moderated the relation between genetic risk and depressive symptom trajectories from age 10/11 to 12/13 using growth mixture modelling. We examined models separately in European American (EA), African American (AA), and Latinx (LX) subgroups of ABCD. Results: In the EA and AA subgroups, adverse life events moderated polygenic scores for GrimAge such that there was increased likelihood of membership in a higher vs. lower depression trajectory. Discussion: We extend literature by identifying genetic contributions to epigenetic aging as a depression diathesis in adolescence. Findings also highlight the detrimental role of adverse life events in exacerbating genetic risk for the development of depression in adolescence.