Registry Study of Parkinson's Disease in Denmark

描述(由申请人提供)：基因-环境相互作用可能是帕金森病(PD)病因的主要因素，然而，由于大多数基于人群的PD研究的样本量相对较小和/或缺乏有效和标准化的跨研究暴露评估，这一研究领域受到了严重阻碍。我们将利用丹麦现有的全球独特资源进行有史以来最大规模的基于人群的病例对照研究，以检查帕金森病的基因与环境的相互作用：丹麦的国家帕金森患者登记册。我们建议从丹麦人群中积极和预期地招募大约2500名最近登记的帕金森病患者和2500名年龄性别匹配的对照组，以收集每次访谈的危险因素信息和用于基因分析的生物材料。所有患者都将由一名训练有素的运动障碍研究员进行临床和表型特征的检查。我们将研究1)哪些终身职业和职业暴露与帕金森病有关；具体而言，我们将评估农业和温室职业(杀虫剂)、金属相关行业(金属和溶剂)和夜班工作(褪黑素水平)；2)某些药物和医疗条件(如非类固醇类药物、阿司匹林和可的松的使用，或M.Crohn和结肠炎和类风湿性关节炎的使用)是否通过其诱导长期低铁水平和诱导/减少全身炎症而与帕金森病呈正或负相关；以及3)先前已确定的因素包括吸烟、饮酒、饮食营养素和污染物(如来自鱼类消费的杀虫剂和金属)以及体力活动。最重要的是，我们将研究代谢和帕金森病特定候选基因的功能多态性是否会对与环境因素相关的风险产生不同的影响。作为第二个目标，我们还将使用被动记录链接，通过唯一ID链接来自国家患者登记册、药房数据库和国家养老基金的数据，以确定这些记录中包含的风险因素信息(例如，职业、药物使用和PD发病前的疾病)，自1983年以来诊断的大约13,000例PD病例和来自丹麦人口的年龄-性别匹配的对照。这项拟议的研究不能在美国进行，因为缺乏人口PD登记可以提供如此大量的病例和有效的方法来控制从普通人口中招募的人员。

DESCRIPTION (provided by applicant): Gene-environment interactions may be major contributors to Parkinson's disease (PD) etiology, however this area of research has been severely hampered by the relatively small sample size of most population-based PD studies and/or a lack of valid and standardized exposure assessment across studies. We will take advantage of a worldwide unique resource available in Denmark to conduct the largest population-based case-control study ever to examine gene-environment interactions in PD: the National Parkinson's Patient Register in Denmark. We propose to recruit actively and prospectively approximately 2500 recently registered incident PD patients and 2,500 age-gender matched controls from the Danish population to collect risk factor information per interview and biological materials for genetic analyses. All patients will be examined and characterized clinically and phenotypically by a trained movement disorder fellow. We will examine 1) which lifetime occupations and occupational exposures are associated with PD; specifically, we will evaluate farming and greenhouse occupations (pesticides), metal related industries (metals and solvents), and night shift work (melatonin levels); 2) whether certain drugs and medical conditions are positively or inversely associated with PD (e.g. NSAIDS, aspirin, and cortisone use, or M. Crohn and colitis and rheumatoid arthritis) through their potential to induce chronically low iron levels and induce/reduce systemic inflammation; and 3) previously identified factors including smoking, alcohol use, dietary nutrients and contaminants (such as pesticides and metals from fish consumption), and physical activity. Most importantly, we will examine whether functional polymorphisms of metabolic and PD specific candidate genes differentially influence risks associated with environmental factors. As a secondary aim we will also employ passive record linkage by unique ID to link data from the National Patient Register, Pharmacy Database, and National Pension fund to identify risk factor information contained in these records (e.g. occupations, medication use, and diseases prior to PD onset) for approximately 13,000 PD cases diagnosed since 1983 and age-gender matched controls from the Danish population. The proposed research cannot be performed in the US due to a lack of population PD registries that would provide access to such a large number of cases and valid methods for control recruitment from the general population.