Genetic and Environmental Modifiers of Parkinson Disease

描述（由申请人提供）：帕金森病（PD）影响大约一百万美国人（Olanow et al. 1998）。考虑到发病率高峰发生在55岁至66岁之间（McDonald etal . 2003），美国人口正在老龄化，PD患病率和随之而来的社会成本预计将上升。破解帕金森病的病因以改善其诊断、治疗和预防是一个极其重要的社会目标。由于遗传和环境因素在疾病过程中都有牵连，对遗传易感性的调查需要考虑环境修饰因子。随着PD家族的大量收集，一氧化氮合成家族的候选基因将通过基于家族的关联测试进行检测；将评估PD风险与环境因素之间的关联，这些因素表明与候选基因有生物学上合理的联系；然后分析遗传因素和环境因素之间的相互作用。由于最合适的方法，遗传和环境的关联和相互作用分析与家庭为基础的数据尚未建立，条件逻辑回归和广义估计方程的经验比较将进行，以提出最合适的分析工具在这方面。

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.