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）病因学的主要因素，然而这一领域的研究受到大多数基于人群的PD研究相对较小的样本量和/或缺乏有效和标准化的研究暴露评估的严重阻碍。我们将利用丹麦全球独一无二的资源，开展迄今为止最大的基于人群的病例对照研究，以检查PD中基因与环境的相互作用：丹麦国家帕金森患者登记处。我们建议积极和前瞻性地从丹麦人口中招募大约2500名最近登记的PD患者和2500名年龄性别匹配的对照组，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。所有患者将由训练有素的运动障碍研究员进行临床和表型检查。我们将研究1)哪些终身职业和职业暴露与PD有关；具体来说，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（如非甾体抗炎药、阿司匹林和可的松的使用，或M. Crohn和结肠炎和类风湿关节炎），通过其潜在的诱导慢性低铁水平和诱导/减少全身性炎症；3)先前确定的因素包括吸烟、饮酒、膳食营养素和污染物（如食用鱼类产生的杀虫剂和金属）以及体育活动。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会影响与环境因素相关的风险。作为次要目标，我们还将采用被动记录链接，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，以识别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），这些记录包括自1983年以来诊断的约13,000例PD病例和来自丹麦人口的年龄性别匹配的对照。拟议的研究不能在美国进行，因为缺乏人口PD登记处，可以提供如此大量的病例和有效的方法来从一般人群中进行对照招募。

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.