EPIDEMIOLOGY AND GENETICS OF PARKINSONS DISEASE

帕金森氏病(PD)的发病率和患病率都在增加 随着老龄化急剧加剧，大约每1000名老年人中就有7人受到影响 40岁及以上，每100名80岁及以上受试者中有3人。这个 这种致残性疾病的原因尚不清楚。这样做的长期目标是 研究是为了澄清现有关于基因作用的争议 与环境因素在帕金森病的病因中的对比。这项研究将 调查与帕金森病家族史相关的帕金森病风险， 阿尔茨海默病、特发性震颤、肌萎缩侧索硬化症或 忧郁症，有抑郁史，头部创伤， 职业性有毒物质接触和吸烟。此外，我们还将研究 家族性帕金森病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。这项研究 设计包括以人群为基础的样本中帕金森病的病例对照研究 和一项基于人群样本的帕金森病遗传研究，该样本由 转诊病人。 病例对照研究将包括#年发生的所有帕金森病事件病例 1976年至1995年间的奥姆斯特德县，通过罗切斯特发现 流行病学项目记录-链接系统(预期N=200)。一个 没有帕金森氏症或其他帕金森症的人口控制将与 每个案例都按年龄和性别分类。对于病例和控制，我们都将收集 有关个人历史和家族历史的信息，请使用 电话采访与住院和门诊患者的摘录 包括在病历链接系统中的病历。一级学位 将约谈病例和对照(预计N=3600人)的亲属 通过电话，合格的亲属将直接接受检查，和/或将 他们的医疗记录被摘录了。分析将以案例为基础- 对照比较和累积发病曲线的比较 帕金森病和其他研究疾病的亲属。这项研究之所以有力，是因为 它包括来自定义人群的所有帕金森病事件；它使用 有代表性的人口控制措施；数据收集从 来源多种多样，部分基于历史数据；该疾病 亲属的身份通过神经学检查和/或 医疗记录。这项研究可以在人群中有效地进行 在奥姆斯特德县，已经建立了记录联系系统， 半个多世纪以来。 基因研究将包括提到的200个基于人群的病例 上图是梅奥诊所周围方圆120英里范围内的200个案例， 来自5个州地区的200例转诊病例(总计N=600例)。这些案件， 他们的配偶(预计N=480)，以及他们的一级亲属 (预计N=5,400)将通过电话和直接面试 只要符合条件，就进行检查。我们将评估家族聚集性是否 帕金森病可用单基因复杂分离来解释 分析。此外，我们将比较遗传聚集性的模式 在基于总体的样本中，有两个转诊样本要处理 可能的推荐偏向。这些研究将极大地有助于 了解帕金森病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.