Prospective studies on Parkinson's disease

帕金森病(PD)是老年人群中第二常见的神经退行性疾病，其病因目前尚不清楚。虽然一些早发性家族性病例已被发现与几个基因有关，但大多数帕金森病病例的病因仍不清楚。由于帕金森病的发病率低、发病隐匿性和临床病程长，对帕金森病环境危险因素的流行病学研究被证明是困难的。 我目前正在进行帕金森氏症基因和环境研究(PAGE)，以调查帕金森病的环境和遗传风险因素。我们利用NIH-AARP饮食和健康研究的基础设施设计了PAGE研究，NIH-AARP饮食和健康研究是大约10年前由国家癌症研究所建立的一个大型癌症队列。在基线时，NCI收集了关于饮食和生活方式的详细信息。在PAGE研究中，我们确认了自己报告的帕金森病诊断，并收集了帕金森病患者和选定的对照组的遗传物质。到目前为止，我们已经成功招募了1100多名潜在的PD患者和1900名对照。与以前的帕金森病流行病学项目相比，PAGE研究是规模最大的，既有DNA，也有预期收集的非遗传暴露。 PAGE研究的主要目标有两个。第一个是通过使用在NIH-AARP卫生署基线调查中收集的暴露数据和在随访中发现的帕金森病病例，前瞻性地检查帕金森病的饮食和生活方式危险因素。除了吸烟和喝咖啡外，没有其他环境风险因素被确定为帕金森病。以往研究的共同局限性是样本量小，并回溯性地收集暴露数据。因此，以前的许多帕金森病研究结果都是粗略的，也是有争议的。有了大的样本量和在PAGE中预期收集的暴露，我们将能够澄清以前的PD发现并识别新的风险因素。第二个主要目的是通过分析帕金森病患者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提供了一个很好的机会来研究基因与环境的相互作用。 此外，我的团队还在与内部和外部调查人员合作开展其他几个项目，以寻找帕金森病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跟踪研究、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.