PROJECT SUMMARY Where one lives is an important contributor to disparities in health behaviors and outcomes, but it has been difficult to draw firm conclusions on the relations between regional/neighborhood context and alcohol use and misuse. This may be because (a) the influence of alcohol use and misuse (and genetic risk for alcohol use and misuse) on where one lives is rarely considered, and (b) the effects of regional/neighborhood contexts may only be relevant for certain genetically vulnerable individuals. Incorporating genetic information into a prospective longitudinal study of the relation between regional/neighborhood context and alcohol use and misuse might resolve inconsistencies in the literature. The proposed research will involve secondary analyses of data from the National Longitudinal Study of Adolescent to Adult Health (AH), which included 20,745 adolescents in 1994-95 and has since conducted four follow-up waves. All five waves of data collection gathered extensive health and behavior information, including alcohol use and misuse; administrative data from the census and other sources were linked to the participants’ home addresses to provide information about the region/neighborhoods in which they lived. Importantly, 9,974 participants provided DNA samples for genotyping, allowing for the quantification of alcohol-related genetic risk by aggregating the effect of individual measured polymorphisms into polygenic risk scores. The inclusion of 1,962 (289 monozygotic twin, 452 dizygotic twin, and 1,251 full sibling pairs) in the sample allows for the control of genetic factors when examining associations between alcohol involvement and regional/neighborhood context and can provide evidence consistent with a potentially causal relation. The three main goals of this proposal are to: (1) examine prospectively the relation between regional/neighborhood contexts and later alcohol use and misuse, and (in adulthood) the prospective relation between alcohol use and misuse and later regional/neighborhood contexts, (2) examine prospectively, within exposure-discordant adult twin and sibling pairs, the relation between regional/neighborhood contexts and later alcohol use and misuse, and the prospective relation between alcohol use and misuse and later regional/neighborhood contexts, (3) examine whether alcohol-related polygenic risk is associated with moving to or remaining in a high-risk neighborhood context and whether alcohol-related polygenic risk amplifies the associations between neighborhood context and alcohol use and misuse. The proposed research has the potential to provide critical insights into how alcohol-related genetic propensities may exacerbate health disparities by influencing whether individuals reside in a high-risk neighborhood context. It will also inform prevention and intervention efforts by clarifying whether the relation between neighborhood context and alcohol misuse involves a direct causal relation. Evidence consis...