A Nationwide Study of Environmental Risk Factors for Parkinson Disease

摘要 帕金森病（Parkinson disease，PD）是第二常见的神经退行性疾病。溶剂、杀虫剂和 金属被怀疑是危险因素，但在这些非常广泛的类别中的具体代理人仍有待确定 最终。流行病学和动物研究共同表明，两个可能的候选人是工业 溶剂三氯乙烯（TCE）和空气中的锰（Mn），一种在一些药物中用作活性成分的金属 农药和化石燃料燃烧过程中释放。然而，很少有关于人类的研究。 这些暴露与PD之间的关系。此外，尽管这些暴露在 环境中，PD和TCE的研究主要集中在职业暴露，而少数环境暴露 PD和空气中Mn的研究产生了相互矛盾的结果。建议的K01职业奖将提供 使用"大数据"和复杂的地理信息系统技术的培训和资源 进行一项关于PD和环境暴露于TCE的大型人群病例对照研究， 使用以前收集的全国范围内的数据和GIS方法来检查这些关联（目的 1和2）及其潜在的相互作用（目标3）。这种方法将使我们能够快速、经济高效地 使用具有地理代表性的病例和对照进行一项具有良好把握度的、基于人群的研究。到 作为对这种高度针对性的方法的补充，我们将采用 建立了从癌症流行病学到相同数据的方法，以确定 美国（探索目标3）。所有的目标都将使用现有的大型病例对照研究（89，790 事件PD病例和> 2200万对照）的Medicare受益人年龄> 65岁，详细（9位邮政编码） 居住数据和人口数据。这项工作将建立在现有的文献和承诺， 产生新的假设的环境原因的一个重要的疾病，已知有一个强大的 环境因素和对症治疗。

Abstract Parkinson disease (PD) is the second most common neurodegenerative disease. Solvents, pesticides and metals are suspected risk factors, but specific agents in these very broad categories remain to be identified conclusively. Epidemiologic and animal studies together indicate that two possible candidates are the industrial solvent trichloroethylene (TCE) and airborne manganese (Mn), a metal used as the active ingredient in some pesticides and released during fossil fuel combustion. However, there have been few human studies on the association between these exposures and PD. In addition, despite these exposures being common in the environment, studies of PD and TCE have focused on occupational exposures, while the few environmental studies of PD and airborne Mn have yielded conflicting results. The proposed K01 career award will provide the training and resources to use “big data” and sophisticated geographic information system (GIS) techniques to conduct a large population-based case-control study of PD and environmental exposure to TCE and airborne Mn using previously collected nationwide data and GIS methods to examine these associations (Aims 1 and 2) and their potential interactions (Aim 3). This approach will allow us to quickly and cost-effectively conduct a well-powered, population-based study with geographically representative cases and controls. To complement this highly targeted approach focused on two common environmental exposures, we will apply established methods from cancer epidemiology to the same data to identify clusters of incident PD within the U.S. (Exploratory Aim 3). All aims will be completed using an existing large case-control study (89,790 incident PD cases and >22 million controls) of Medicare beneficiaries age >65 with detailed (9-digit zip code) residence data and demographic data. This work will build substantially on existing literature and promises to generate novel hypotheses on the environmental causes of an important disease known to have a strong environmental component and only symptomatic treatment.