Project Summary The current renewal proposal seeks to expand upon our successful initial award to clarify the mechanisms underlying observed associations between alcohol use disorder (AUD) and suicidal behaviors (SB), including non-fatal suicide attempts and suicide death. The research team has an extensive history of productive collaborations, including in the realm of psychiatric and substance use disorder research. We have access to longitudinal Swedish national registries including medical, criminal, census, family, and socioeconomic data for nearly 11 million individuals; these resources will be linked to create detailed datasets encompassing a wide range of risk factors at individual, familial, and environmental levels. We will utilize these resources to extend our prior research through the pursuit of four specific aims. In the first aim we will evaluate how AUD and post- traumatic stress disorder, or trauma exposure, relate via mediating or moderating pathways to risk of SB. We will apply well-established methods, including those that facilitate causal inference. Second, we will directly compare and contrast pathways to SB via AUD versus major depression (MD). AUD and MD constitute two primary correlates/risk factors for SB, but much remains unknown about distinctions and commonalities between these associations. The current proposal will focus primarily on the role of social dysfunction, with the goal of identifying factors that may improve risk assessment. Third, we will consider how AUD relates to two common medical conditions, cardiovascular disease and dementia, with respect to SB risk. Both conditions are themselves associated with increased SB risk but whether they mediate and/or exacerbate the impact of AUD is not known. Finally, we will leverage our expertise in genetic epidemiology by pursuing analyses that will clarify how aggregate genetic liability to AUD or SB, versus AUD and SB, is differentially related to psychopathology and other correlates of risk. Critically, Sweden and the US have comparable rates of suicidal behavior and share many characteristics, including an ethnically and socioeconomically diverse population; however, the US lacks registry resources comparable to those available in Sweden. We expect that the statistical power of these registries, in conjunction with the research team’s extensive expertise in psychiatric and substance abuse research, social and genetic epidemiology, and causal modeling, will yield substantive findings on the relationship between AUD and SB, with important implications for improving our efforts at SB prevention and intervention.