The Buffering Effects of Resilience on Alcohol Use: A Phenotypic and Genotypic Investigation

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PROJECT SUMMARY The college years encompass a time of vulnerability for problematic alcohol use/alcohol use disorder (AUD) and trauma exposure, which is a transdiagnostic risk factor for AUD, posttraumatic stress disorder (PTSD), and comorbid AUD-PTSD. However, not all who experience a traumatic event develop these disorders, highlighting the need to identify factors that impact post-trauma outcomes. Resilience has been shown to buffer the effects of new onset trauma on alcohol use problems. To date, there are no existing studies longitudinally examining the buffering effects of resilience on alcohol use outcomes in the face of new onset trauma in a college-aged sample. Resilience is moderately heritable, but further research is needed to examine this heritability using molecular approaches (i.e., genome-wide complex trait analysis; GCTA) and its genetic architecture through identifying individual variants associated with resilience (i.e., genome-wide association studies; GWAS). Resilience also demonstrates genetic overlap with internalizing and externalizing disorders, including AUD. This overlap has not been examined using a molecularly informed design, warranting molecular genetic investigation of the etiologic overlap between AUD and resilience. The proposed study aims to fill these voids using a genetically informative longitudinal cohort study from a large urban university (NIAAA-R37 AA011408) to achieve three primary aims: 1) investigate the buffering effect of resilience against new onset traumatic events on alcohol use phenotypes; 2) examine the overall heritability of resilience (i.e., GCTA), as well as identify individual variants (i.e., GWAS); and 3) examine the aggregate genetic overlap of resilience with alcohol use phenotypes, PTSD, and other protective factors (e.g., subjective well-being), using aggregate risk analyses (i.e., polygenic risk scores). Study findings will provide insight into the longitudinal buffering effect and etiologic underpinnings of psychiatric resilience as well as the shared genetic risk between resilience, AUD, and PTSD, which will greatly inform prevention and intervention efforts. The present proposal seeks to meet four training goals, developed in collaboration with the mentorship team: 1) develop expertise in the empirical study of trauma-related phenotypes (i.e., AUD); 2) develop expertise in longitudinal statistical modeling of phenotypic data; 3) obtain advanced training in statistical methods for analysis of molecular genetic data; 4) continue to build professional development skills that will strengthen my background and support my development into a well-rounded academic researcher, as well as enhance my ongoing clinical training. The proposed research and training aims align well with the National Institute on Alcohol Abuse and Alcoholism’s (NIAAA) mission, emphasizing clinically relevant, transdisciplinary research. These research and training aims also align with the NIAAA Strategic Objective to “identify behavioral and biological markers of alcohol use and alcohol-related conditions, develop and optimize methods for assessing these markers, and establish precise estimates of alcohol use, misuse, and related conditions.”