Registry Study of Parkinsons 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）病因的主要贡献者，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，该研究领域受到严重阻碍。我们将利用丹麦的全球独特资源进行有史以来最大的基于人群的病例对照研究，以检查PD中的基因-环境相互作用：丹麦的国家帕金森病患者登记。我们建议积极和前瞻性地从丹麦人群中招募约2,500名最近登记的PD患者和2,500名年龄性别匹配的对照，以收集每次访谈的风险因素信息和用于遗传分析的生物材料。所有患者将由一名经过培训的运动障碍研究员进行临床和表型检查和表征。我们将检查1）哪些终生职业和职业暴露与PD相关;具体而言，我们将评估农业和温室职业（农药），金属相关行业（金属和溶剂）和夜班工作（褪黑激素水平）; 2）某些药物和医疗条件是否与PD呈正相关或负相关（例如NSAIDS，阿司匹林和可的松的使用，或M。克罗恩病、结肠炎和类风湿性关节炎）通过它们诱导慢性低铁水平和诱导/减少全身炎症的潜力;和3）先前确定的因素，包括吸烟、饮酒、膳食营养素和污染物（如杀虫剂和来自鱼类消费的金属）和身体活动。最重要的是，我们将研究代谢和PD特异性候选基因的功能多态性是否差异影响与环境因素相关的风险。作为次要目的，我们还将通过唯一ID采用被动记录链接，以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，以确定自1983年以来诊断的约13，000例PD病例和丹麦人群年龄性别匹配对照的这些记录中包含的风险因素信息（例如，职业、药物使用和PD发作前的疾病）。由于缺乏人群PD登记研究，无法在美国进行拟定的研究，该登记研究可提供从普通人群中招募对照病例的大量病例和有效方法。

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.