PROJECT SUMMARY/ABSTRACT
Alcohol is the most widely used substance and the third-leading preventable cause of death in the United
States. Initiation of alcohol use typically occurs in adolescence, and early onset alcohol use (< age 15) has
been associated with prolonged negative outcomes such as increased risk for AUD. The development of
alcohol use and AUD is influenced by genetic and environmental factors, and the complex interactions among
them (i.e., gene-environment interaction or GE). Yet, the majority of genetic and GE research has been 1)
conducted with populations of European ancestry, and 2) focused on alcohol outcomes among individuals who
have already initiated alcohol use or developed AUD. Thus, there is limited understanding of GE processes in
racially-ethnically diverse populations, and how genetic risk manifests earlier in development in order to inform
early prevention and intervention efforts. Furthermore, despite culture being an important context that shapes
human behavior, cultural risk and protective factors have been largely overlooked in GE research. We seek to
advance the understanding of etiology of alcohol use and AUD among racially-ethnically diverse populations
by taking a developmentally and culturally informed approach to study GE processes. This project draws data
from the ongoing Adolescent Brain and Cognitive Development (ABCD) Study, which includes rich genomic
and phenotypic data from a longitudinal sample (N = 11,875; 52.1% White, 15.0% Black, and 20.3%
Hispanic/Latinx) of racially-ethnically diverse children from late childhood (9-10 years old) through
adolescence. The project examines three research aims. First, we will characterize polygenic influences on
adolescent alcohol use among racially-ethnically diverse youth. Using a genome-wide polygenic score (PRS)
approach, we will examine the effects of multiple adult and child-based PRS for alcohol and related traits (e.g.,
externalizing, internalizing symptoms) on timing of progression through the stages (e.g., experimentation,
initiation, regular use, and problematic use), and trajectories of alcohol use from late childhood to adolescence.
Second, we will examine the role of multiple childhood precursors (i.e., impulsivity, externalizing, and
internalizing symptoms) in mediating polygenic influences on alcohol use. Finally, we will investigate the role of
cultural-contextual risk and protective factors (i.e., parenting, peer deviance, stressful life events, racial
discrimination experiences, familism cultural value) in moderating genetic influences on childhood precursors
and adolescent alcohol use. We will explore how the associations of genetic, cultural-contextual factors,
childhood precursors, and alcohol use change from late childhood to adolescence by examining age and
developmental differences, and exploring differences by sex and pubertal status. Findings will advance alcohol
and health disparities sciences by elucidating developmental and environmental mechanisms linking genetic
risk to alcohol use among racially-ethnically diverse adolescents, providing critical insights for alcohol use
prevention and intervention programs, including who is most at risk, what to target, and when to intervene.
