EPIDEMIOLOGY AND GENETICS OF PARKINSONS DISEASE

帕金森病（Parkinson's disease，PD）的发病率和患病率均呈上升趋势 随着年龄的增长，每1 000人中约有7人受到影响， 40岁及以上，80岁及以上受试者中有3例。的 这种致残性疾病的原因尚不清楚。长期目标是 研究是为了澄清现有的关于遗传作用的争议， 与环境因素在PD病因学中的作用。 这项研究将 调查与PD家族史相关的PD风险， 阿尔茨海默病、特发性震颤、肌萎缩侧索硬化症，或 抑郁症，并且有抑郁症，头部创伤， 职业中毒和吸烟。此外，我们会研究 家族内PD和其他相关疾病的遗传分离 以及遗传和环境因素之间的相互作用。研究 设计包括一项基于人群样本的PD病例对照研究 以及一项基于人群样本的PD遗传研究， 转诊病人。 病例对照研究将包括所有发生在以下人群中的PD事件病例： 奥姆斯特德县在1976年和1995年之间，并确定通过罗切斯特 流行病学项目记录链接系统（预期N = 200）。一 无PD或其他帕金森综合征的人群对照将与 每一个病例都按年龄和性别分类。对于病例和对照组，我们将收集 关于个人历史和家族史的信息， 电话访问和住院和门诊病人的摘要 将医疗记录纳入记录连接系统。一级 将对病例和对照组（预期N = 3，600）的亲属进行访谈 通过电话，符合条件的亲属将直接接受检查，和/或将 提取他们的医疗记录分析将基于案例- 对照比较和累积发病率曲线比较 PD和其他研究疾病的亲属。这项研究是强有力的，因为 它包括来自定义人群的所有PD事件病例;它使用 代表性群体对照;数据收集来自 多个来源，部分基于历史数据;和疾病 亲属的状况通过神经系统检查和/或 医疗记录本研究可在人群中有效进行 奥姆斯特德县的记录链接系统已经到位， 超过半个世纪。 这项遗传学研究将包括上述200例基于人群的病例 上面，200例病例来自马约诊所周围120英里的半径， 200例来自5个州的地区（总N = 600）。这些案件， 他们的配偶（预期N = 480）和他们的一级亲属 （预计N = 5，400）将通过电话和直接访谈 只要符合条件就检查。我们将评估是否有家族聚集性 PD可以用一个主基因进行复杂分离来解释 分析。 此外，我们将比较遗传聚类的模式， 在基于人口的样本中， 可能存在推荐偏倚。这些研究将大大有助于 了解PD的原因和可能的预防措施。

Both the incidence and prevalence of Parkinson's disease (PD) increase steeply with aging, affecting approximately 7 per 1,000 individuals aged 40 years and over, and 3 per 100 subjects aged 80 years and over. The causes of this disabling disease are unknown. The long term goal of this research is to clarify the existing controversy on the role of genetic versus environmental factors in the etiology of PD. The study will investigate the risk of PD associated with a family history of PD, Alzheimer's disease, essential tremor, amyotrophic lateral sclerosis, Or depression, and with a personal history of depression, head trauma, occupational toxic exposures, and smoking. In addition, we will study the genetic segregation of PD and other associated disorders within families and the interaction between genetic and environmental factors. The study design consists of a case-control study of PD in a population-based sample and a genetic study of PD in a population-based sample augmented by referral patients. The case-control study will include all incident cases of PD occurring in Olmsted County between 1976 and 1995 and identified through the Rochester Epidemiology Project records-linkage system (expected N = 200). A population control free of PD or other parkinsonism will be matched to each case by age and gender. For both cases and controls, we will collect information regarding personal history and family history using a telephone interview and the abstracting of inpatient and outpatient medical records included in the records-linkage system. First-degree relatives of cases and controls (expected N = 3,600) will be interviewed via telephone, eligible relatives will be examined directly, and/or will have their medical records abstracted. Analyses will be based on case- control comparisons and on the comparison of cumulative incidence curves of PD and other study diseases in relatives. This study is strong because it includes all incident cases of PD from a defined population; it uses representative population controls; data collection is obtained from multiple sources and is partly based on historical data; and the disease status of relatives is confirmed through neurologic examination and/or medical records. This study can be conducted efficiently in the population of Olmsted County where a records-linkage system has been in place for more than half a century. The genetic study will include the 200 population-based cases mentioned above, 200 cases referred from a 120-mile radius around the Mayo Clinic, and 200 cases referred from a 5-state region (total N = 600). These cases, their spouses (expected N = 480), and their first-degree relatives (expected N = 5,400) will be interviewed via telephone and directly examined whenever eligible. We will assess whether familial clustering of PD can be explained by a single major gene using complex segregation analyses. in addition, we will compare the pattern of genetic clustering in the population-based sample with the two referral samples to address possible referral bias. These studies will contribute greatly to understanding the causes and possible prevention of PD.