Genetic and Environmental Modifiers of Parkinson Disease

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DESCRIPTION (provided by applicant): Parkinson Disease (PD) affects approximately one million Americans (Olanow et al. 1998). Considering peak incidence occurs between ages 55 and 66 (McDonald et al. 2003) and the U.S. population is aging, PD prevalence and ensuing societal costs are expected to rise. Deciphering the etiology of PD to improve its diagnosis, treatment, and prevention is a societal goal of utmost importance. As genetic and environmental factors have been implicated in the disease process, investigation into genetic susceptibility requires consideration for environmental modifiers. With a large collection of PD families, candidate genes of the nitric oxide synthesizing family will be examined with family-based association tests; associations between PD risk and environmental factors that demonstrate a biologically plausible link to the candidate genes will be assessed; and interactions between the genetic and environmental factors will then be analyzed. Since the most appropriate method for genetic and environmental association and interaction analyses with family- based data is not yet established, an empirical comparison of conditional logistic regression and generalized estimating equations will be performed to propose the most appropriate analytic tool in this context.