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等人。1998年)。考虑到发病高峰发生在55岁至66岁之间(McDonald等人。2003年)，美国人口老龄化，帕金森病患病率和随之而来的社会成本预计将上升。破译帕金森病的病因以改进其诊断、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有牵连，对遗传易感性的研究需要考虑环境修饰物。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查；将评估PD风险与证明与候选基因有生物学上可信联系的环境因素之间的关联；然后将分析遗传因素和环境因素之间的相互作用。由于基于家庭数据的遗传与环境关联和交互作用分析的最合适方法尚未建立，因此将对条件Logistic回归和广义估计方程进行实证比较，以提出在此背景下最合适的分析工具。

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.