Genetic and Environmental Modifiers of Parkinson Disease

描述（由申请人提供）：帕金森病（PD）影响约100万美国人（Olanow et al. 1998）。考虑到发病率高峰发生在55 - 66岁之间（McDonald et al. 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。破译PD的病因，以改善其诊断，治疗和预防是一个至关重要的社会目标。由于遗传和环境因素与疾病过程有关，因此对遗传易感性的研究需要考虑环境因素。在大量收集PD家族的情况下，将使用基于家族的关联测试来检查一氧化氮合成家族的候选基因;将评估PD风险与环境因素之间的关联，这些因素证明与候选基因存在生物学上合理的联系;然后将分析遗传因素与环境因素之间的相互作用。由于尚未建立最合适的方法，遗传和环境的关联和相互作用的分析与家庭为基础的数据，条件logistic回归和广义估计方程的实证比较，将在这种情况下提出最合适的分析工具。

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.