Prospective studies on Parkinson's disease

帕金森氏病（PD）是老年人群中第二大最常见的神经退行性疾病，其原因在很大程度上是未知的。虽然已经确定了几个基因负责一些早发性家族性病例，但大多数PD病例的原因仍不清楚。由于帕金森病发病率低、起病隐匿、临床病程长，对帕金森病环境危险因素的流行病学研究比较困难。 我目前正在进行帕金森氏症基因和环境研究（PAGE），以调查PD的环境和遗传风险因素。我们设计了PAGE研究，利用了NIH-AARP饮食和健康研究的基础设施，这是一个由国家癌症研究所在大约10年前建立的大型癌症队列。在基线时，NCI收集了有关饮食和生活方式的详细信息。 在PAGE研究中，我们正在确认自我报告的PD诊断，并从PD病例和选定的对照组中收集遗传物质。到目前为止，我们已经成功招募了1,100多名潜在的PD患者和1,900名对照。与以前的PD流行病学项目相比，PAGE研究是最大的DNA和前瞻性收集的非遗传暴露。 PAGE研究有两个主要目标。第一个是通过使用在NIH-AARP DH基线调查中收集的暴露数据和随访期间确定的PD病例，前瞻性地检查PD的饮食和生活方式风险因素。除了吸烟和喝咖啡外，尚未确定PD的其他环境风险因素。以往研究的常见局限性是样本量小和回顾性收集的暴露数据。因此，许多以前的PD结果是粗糙和有争议的。通过大样本量和前瞻性收集的PAGE暴露量，我们将能够澄清先前的PD结果并识别新的风险因素。第二个主要目的是通过分析PD病例和对照的遗传数据来研究基因和基因-环境相互作用的作用。 大样本量和系统收集的暴露量为研究基因-环境相互作用提供了良好的机会。 此外，我的团队还与校内和校外的研究人员合作开展了一些其他项目，以寻找PD和其他神经退行性疾病的原因。这些研究包括卫生专业人员随访研究、护士健康研究、癌症预防研究II营养队列和社区关节硬化症风险研究。

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in the elderly population and its causes are largely unknown. Although several genes have been identified to be responsible for some of the early onset familial cases, the causes for most PD cases remain unclear. Epidemiological studies on PD environmental risk factors are proven difficult, due to the low incidence, the insidious onset and the clinical course of the disease. I am currently conducting the Parkinson's Genes and Environment Study (PAGE) to investigate environmental and genetic risk factors for PD. We designed the PAGE study by taking advantage of the infrastructure of NIH-AARP Diet and Health Study, a large cancer cohort that was established by the National Cancer Institute about 10 years ago. At baseline, NCI collected detailed information on diet and lifestyle. In the PAGE study, we are confirming self-reported PD diagnoses and collecting genetic materials from PD cases and selected controls. To date, we have successfully recruited over 1,100 potential PD patients and 1,900 controls. Compared with previous PD epidemiological projects, the PAGE study is the largest with both DNAs and prospectively collected non-genetic exposures. There are two primarily goals of the PAGE study. The first is to examine prospectively diet and lifestyle risk factors for PD, by using exposure data collected at NIH-AARP DH baseline surveys and PD cases identified during the follow-up. Other than smoking and coffee drinking, no other environmental risk factors for PD have been established. Common limitations of the previous studies are small sample size and retrospectively collected exposure data. Therefore many of the previous PD findings are crude and controversial. With a large sample size and prospectively collected exposures in PAGE, we would be able to clarify previous PD findings and identify novel risk factors. The second primary aim is to investigate roles of genes and gene-environment interactions by analyzing genetic data from PD cases and controls. The large sample size and systematically collected exposure offer a good opportunity to investigate gene-environment interactions. In addition, my group is also working on a few other projects in collaboration with intra- and extramural investigators to search for causes of PD and other neurodegernerative diseases. These studies include the Health Professionals Follow-up Study, the Nurses Health Study, the Cancer Prevention Study II Nutrition Cohort, and the Arthrosclerosis Risk in Community Study.