This R25 application seeks a final 5 years to continue development of a research education program (REP) focused on training in the development of computational, and statistical tools or methods to advance human addiction genetic research. By making such tools widely available (after appropriate pretesting and QC) and training a new generation of computational/statistical scientists motivated to pursue problems in addiction genetics research, the program seeks both to maximize the payoff from existing GWAS and genetic epidemiologic studies of substance use (`addiction') disorders, and to facilitate new directions in human addiction genomics research (e.g., emphasizing epigenetic mechanisms, tissue or cell-specific effects). Consistent with the flexibility of the R25 (compared to T/F) mechanisms, the non-traditional backgrounds of postdoctoral trainees (e.g., bioinformatics, computer science, statistical genetics), and the requirement to produce and share innovative tools and methods, the REP proposes a 4-year training model with 3 existing postdocs, and 4 new postdocs to be recruited during the first two years of award. The program recruits postdoctoral trainees globally to identify candidates of exceptional talent and energy, and pairs them with an exceptional, diverse and highly collaborative faculty, reflected in the significant an highly innovative contributions of current and former trainees (e.g., 0.5 million hits per month fo one web-based tool). The program takes advantage of an exceptional institutional environment, Washington University being a leader in genomics research (including epigenomics), in statistical genetics and genomics, and in biological psychiatry research (including psychiatric - and especially addiction - genetics research). It uses a research apprenticeship training model, in which a trainee is paired with a primary mentor with pertinent expertise in computational biology/statistical genomics or genetics research who has identified a problem that can advance human addiction genetics research; one or more co-mentors with strong backgrounds as clinical researchers focused on addiction genetics; and external consultants who can supplement the expertise of the mentoring team (e.g., animal models). Formal coursework at Washington University and workshops attended elsewhere in addiction research, in responsible conduct of research, and other didactics tailored to strengthen academic background (e.g., genomics, computer science) are used to advance the research education of individual postdoctoral trainees. The program is led by directors with backgrounds in addiction genetics, statistical genetics/genomics and computational biology with histories of successful collaboration. The implementation and refinement of the REP is guided by a strong Internal Program Advisory Committee with annual feedback and critique from an outstanding External Advisory Board, and from consultant participants in biennial postdoctoral symposia. We promote ongoing collaboration of addiction, statistical genetics and computational biology scientists in research and in research education beyond the life of the R25.
Illicit drug and tobacco dependence (`addiction') represent a considerable personal, family and public health burden. The important role of individual genetic vulnerability in contributing to addiction risk is well established, but progress in human addictio genetic research in identifying specific genetic mechanisms, and success in translating findings to develop new therapeutic approaches, has been quite modest. This research education program seeks to develop computational and statistical tools, which can be widely used by addiction genetic and other researchers, in order to both maximize existing investments in genomic and genetic epidemiologic studies of addictive disorders, and help advance human addiction genetics/genomics research in new directions.
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