Project Summary Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) commonly co-occur, and this comorbidity is associated with higher consumption, treatment dropout, and risk for relapse. Urban populations of low socioeconomic status are particularly at risk for AUD and PTSD. Research on the etiology of co-occurring AUD and PTSD is needed in these understudied and low resourced populations to help address a disparity in the knowledge base. Directional models of comorbidity exist, self-medication and susceptibility, although there are major gaps (e.g., few studies testing direction of causation and or bidirectionality effects, lack of specificity of assessment, lack of test of sex effects). Additionally, comorbidity could be influenced by genetic risk as both AUD and PTSD are moderately heritable, overlap in latent genetic risk, and are genetically correlated in large genome wide association studies (GWAS; rG=0.35). Black persons are underrepresented in genetics research, and thus, genetically informed studies in this population are critically needed for equity in knowledge gained in this area. The current multi-method study will fill these gaps by conducting a genetically informative ecological momentary assessment (EMA) study using a longitudinal measurement burst design. Participants recruited through the Grady Trauma Project (GTP), which consists of high-risk inner-city residents. We will enroll a sample of 400 individuals and they will be asked to provide: clinical interview diagnostic data on PTSD, AUD, and comorbidities, detailed self-report measures including trauma history, social determinants of health, other risk and protective factors, and a saliva sample for GWAS. The EMA protocol will capture the temporal relations between PTSD and alcohol use phenotypes (e.g., consumption, binge, AUD symptoms, craving) and clarify not only who is at risk, but when the risk behaviors occur. Analyses will simultaneously test all three models of comorbidity (i.e., self-medication, susceptibility, shared risk) and will test for sex specific pathways. Following this initial period of EMA, a measurement burst design consisting of three EMA bursts, each spaced two months apart, will occur to examine the impact of time varying social determinants of health (e.g., new trauma, financial stress, racial discrimination) on the functional relationships found in the first aim. Lastly, the exploratory aim will conduct genome wide analyses with a focus on a novel multivariate genetic method, genomic Structural Equation Modeling (gSEM), which will be used to produce polygenetic risk scores (PRS) that index genetic risk for comorbidity of PTSD and AUD, and unique risk for each condition. PRS indexing shared risk between AUD- PTSD, unique to AUD, and unique to PTSD, will be incorporated into the best fitting models from the EMA analyses to determine if the phenotypic relations found are influenced by genetic risk. This study will advance our understandi...