) The major goal of the Genetic Epidemiology Core is to provide the conceptual basis and methodology to investigate the role of environmental and genetic risk factors and their joint contribution to the development of nicotine dependence. Limitations in our basic knowledge regarding the recurrence risk of tobacco dependence in families, patterns of familial aggregation of tobacco dependence, as well as the extent to which wholly environmental factors may induce this phenotype render any attempt to identify susceptibility genes premature. To date, there is not a single published controlled family study of nicotine-related phenotypes using contemporary family study methodology. Identifying the role of susceptibility genes underlying complex phenotypes such as tobacco use require basic knowledge in several disciplines including epidemiology, behavior genetics, molecular genetics, statistical genetics, and population genetics. Progress achieved in each of these areas specifically deviated to enhancing our understanding of the phenotype and genotypes of relevance to nicotine dependence will enable us to develop a comprehensive conceptualization of the influence of genetic factors at each stage of the development of tobacco dependence. Even without the identification of specific genes, the genetic epidemiology perspective provides a powerful approach to integrate familial and individual risk factors that influence nicotine use, and may lead to the identification of targets for prevention. The specific goals of our core will be to: (1) centralize assessment of family history, accurate collection of pedigree information, and ethnicity; (2) examine a wealth of existing data available from study investigators across the entire center to refine phenotypic definitions and identify sources of complexity of the familial aggregation of smoking; (3) develop and apply analytic methods on patterns of familial aggregation and the environmental contexts of nicotine outcomes in the core resource of community based probands and families that form the central basis for this center; (4) conduct basic research on candidate genes for nicotine dependence and statistical models for family-based association studies that reflect the complexity of this phenotype in preparation for identifying genes in the core data from the present application; and (5) provide training for center investigators and trainees in the concepts and methods of genetic epidemiology.
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