Program Director/Principal Investigator: Kendler, Kenneth S This second competitive renewal seeks to continue our innovative and productive research program which seeks to understand the etiology of drug use disorders (DUD) utilizing data available on the entire population of Sweden of unparalleled completeness and depth. We have eight specific aims: i) to use a newly developed genetic risk score for DUD for the entire Swedish population to explore boundaries of the DUD phenotype, model gene x environment interactions and clarify origins of DUD-related comorbidities; ii) to understand the impact of social roles/relationships (e.g., marriage, divorce, parenthood) on risk and resilience for DUD; iii) to explore the etiology of opiate use disorder (OUD) by comparing the social, familial and genetic risk factors OUD and non-opiate DUD, by clarifying the etiologic role of opiate prescriptions in OUD development and to identify clinically meaningful subtypes of OUD, especially an iatrogenic form; iv) to investigate the impact of institutional settings on subsequent DUD, focusing on military service and incarceration; v) to evaluate the impact of synthetically constructed populations compared to actual Swedish populations in the evaluation of DUD and OUD utilizing FRED (A Framework for Reconstructing Epidemiological Dynamics) developed by our collaborators at the Public Health Dynamics Laboratory (PHDL) at University of Pittsburgh; vi) to improve our contagion models for the transmission of DUD by taking advantage of new data available in Swedish registries on high school attendance, college attendance and workplace, improved Geographic Information Systems and FRED; vii) to explore the association between stressful and traumatic events including COVID-19 exposure severity and stress-related disorders (e.g., posttraumatic stress disorder [PTSD]) with DUD onset and recurrence and examine moderators of impact of both exposures and stress-related disorders on DUD and viii) using a calibrated, detailed version of the Swedish population in FRED, to evaluate the predicted impact of a range of mitigation strategies, based on the relationships defined by our earlier work and new findings from the above aims. We will, for many of these aims, attempt to clarify the causal nature of the observed associations using statistical and natural experimental methods. We will use comprehensive data from multiple nationwide data sources in Sweden on 11.8 million men and women to accomplish these goals. Applying the deep expertise of our research groups at Virginia Commonwealth, PHDL and Lund University in drug abuse research, social and genetic epidemiology, causal inference and epidemiological model development to a uniquely powerful sample, we expect this study to have important implications for DUD research, prevention and policy.
Kendler, Kenneth S Project Narrative ? This project seeks to clarify etiologic pathways to aggregate drug abuse and opiate abuse more specifically. To accomplish this goal, we will utilize a unique and growing set of epidemiological resources available in the country of Sweden and a range of advanced statistical modeling methods. The resulting findings will be relevant to the US and other developed countries, with potential impacts on drug abuse prevention, treatment and policy.
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