This is a competing renewal of Gene-Environment Interaction in Adolescent Alcohol Use (R01AA015416), a new investigator research grant that used data from a longitudinal, population-based Finnish twin study to characterize the extent and nature of gene-environment interactions on substance use and externalizing behavior across adolescence. Our analyses demonstrated that etiological factors impacting substance use and externalizing behavior in adolescence vary profoundly as a function of the environment. In this competing renewal, we propose to use data now available on the twins in the young 20s (range 21-27 years) to characterize gene-environment interplay across the transition to young adulthood. The young 20s is a period of critical change as new environments become developmentally relevant (e.g., romantic partnerships, continuation vs. cessation of education, joining the workforce, having children). It also represents a critical time for the development of risky alcohol use behaviors and the onset of problems. This application, prepared by a team of investigators from Virginia Commonwealth University, the University of Helsinki, and Indiana University, has three specific aims. The first aim is to use twin data to characterize gene-environment processes (both gene-environment correlation and interaction) on substance use and externalizing behavior in young adulthood. The second aim is to conduct a series of exploratory analyses aimed at understanding how gene-environment interaction effects identified in twin data can inform our understanding of GxE effects associated with measured genes. We will test whether environments that moderate latent genetic risk in the twin analyses also moderate the association between specific individual genotypic risk and outcome. The third aim is to test the generalizability of identified gene environment interaction effects in a second, independent sample, the Virginia Twin Study of Adolescent Behavioral Development, with phenotypic data collection across a parallel age range from adolescence to young adulthood, and GWAS data. Together, these analyses will advance our understanding of how genetic and environmental influences come together to contribute to substance use patterns during the high-risk young adulthood developmental phase.