Genetics of PTSD and Trauma-Related Drinking

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PROJECT SUMMARY Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are prevalent, costly to society, and frequently co-occur. In fact, nearly half of individuals in treatment for AUD meet diagnostic criteria for current PTSD. Both AUD and PTSD are moderately heritable and have overlapping latent genetic risk; however, etiological models examining the shared risk between these phenotypes are lacking. The drinking to cope self- medication model is a promising paradigm to inform research in this area. Although it is well accepted that coping-oriented drinking is linked with problematic alcohol use and increased likelihood of AUD, there is a paucity of research examining drinking to cope with trauma-related symptoms specifically. To date, there are no studies, phenotypic or genetic, on trauma-related drinking to cope. The present study seeks to fill this void by leveraging a genetically informative longitudinal cohort study from a large urban university (NIAAA-R37 AA011408) in order to achieve three primary aims: 1) examine the relationships between AUD symptoms, trauma-related drinking to cope, and PTSD symptoms and determine if trauma-related drinking to cope mediates the relationship between PTSD and AUD symptoms; 2) examine genetic variation (i.e., genome wide association [GWA] analyses) and aggregate risk (i.e., genome wide complex trait analyses [GCTA], polygenic risk score [PRS]) associated with trauma-related drinking, PTSD, and shared variation between the two phenotypes; and 3) apply bioinformatics tools to investigate genetic pathways associated with, and probable overlap between, trauma-related drinking and PTSD. The results of this study will aid in elucidating shared genetic influences underlying trauma-related drinking and PTSD, an area which remains poorly understood. The ability to identify individuals with higher biological risk for trauma-related drinking and PTSD will inform targeted prevention and integrative intervention strategies, particularly among individuals at increased psychosocial risk for problematic alcohol use and PTSD, such as college-age populations. The proposed NRSA study has been developed with four specific training goals in mind: 1) develop expertise in the empirical study of trauma-related phenotypes (e.g., AUD, trauma-related drinking, PTSD); 2) gain a solid foundation in molecular and statistical genetics; 3) gain knowledge and experience in bioinformatics techniques, such as genetic pathway analyses; and 4) further cultivate professional development skills that will enhance the candidate’s background in support of becoming a knowledgeable and well-rounded academic researcher. These research and training aims reflect the National Institute on Alcohol Abuse and Alcoholism’s (NIAAA) mission, which emphasizes clinically relevant, transdisciplinary research, as well as directly align with the NIAAA Strategic Objective to “identify genes associated with vulnerability for alcohol dependence by employing new and emerging technologies, particularly on samples from study populations previously recruited for genetic research on alcohol dependence.” !