The Genetic Epidemiology of Nicotine Dependence

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DESCRIPTION (provided by applicant): This K07 award proposal provides the training and research activities required for Dr. Helena Furberg, a classically trained cancer epidemiologist, to become an independent genetic epidemiologist in tobacco prevention and control research. Given the complexity of nicotine dependence, and the rate at which genomic data are becoming available for use in epidemiological studies, Dr. Furberg must develop a deep knowledge and expanded skill set in order to design, conduct, analyze, interpret, and disseminate this information appropriately. During five years of the award, she seeks formal training in specific areas that complement her background in cancer epidemiology: 1) the nicotine dependence phenotype, 2) molecular genetics, 3) statistical genetics, and 4) the ethical, legal, and social implications of human genetic research. The activities proposed during the five years of the award challenge her intelligently through expert mentor involvement in all four substantive areas, relevant coursework and workshops, and attendance at key national meetings. The knowledge she acquires through the training activities will be applied directly to a genetic epidemiology study of nicotine dependence, nested within a large NCI-funded study of smoking cessation (PI: Dr. Patrick Sullivan, primary mentor on this award). Detailed tobacco use data and DNA specimens will be available on 2,000 Swedish individuals between 25 and 47 years of age. Dr. Furberg proposes to genotype ~70 genetic markers in four rational candidate genes and evaluate associations in relation to nicotine dependence. The training she receives in addiction biology and tobacco use assessment will help her accurately classify nicotine dependence and consider relevant confounders, training in genetics will inform her selection of plausible candidate genes, training in statistical genetics will teach her how to integrate genetic information into a large association study adequately powered to address the research questions, and ELSI training will assist her in thoughtfully interpreting and disseminating the results. An increased understanding of the mechanisms involved in nicotine dependence could lead to more effective treatment efforts, and consequently contribute to a decrease in the prevalence of tobacco-related illnesses in our society. The skills Dr. Furberg will acquire from this K award are life-long and will position her to become an independent investigator who collaborates intelligently and creatively with researchers in different fields, an approach that is critical for progress against all cancers. Public Health Relevance: In order to achieve reductions in cancer morbidity and mortality, increased knowledge about the genetics of nicotine addiction are needed. Findings from this research project will contribute information on genetic reasons for individual differences in nicotine addiction, which could lead to more effective treatment efforts for cigarette smoking.