Epidemiology of Dystonia in a Multi-Ethnic Population

描述（由申请人提供）：肌张力障碍是一种致残的神经退行性疾病，引起持续的不随意肌收缩，产生扭曲、重复和模式运动或异常姿势。虽然它是第三种最常见的运动障碍，但人们对肌张力障碍发生的民族或种族差异或危险因素知之甚少。为了解决这个问题，我们将从一个大型的多种族（约40%非白人）健康维护组织中大约300万人中确定一个肌张力障碍事件队列。我们预计将发现至少1000例原发性扭转肌张力障碍（PTD）。这将构成迄今为止参加流行病学研究的最大的PTD患者群体，并将首次为解决有关肌张力障碍流行病学的一些问题提供基础。本应用程序的第一个目的是估计PTD的总体发病率和患病率以及临床定义的亚型（包括广泛性、颅脑、颈椎、肢体和喉肌张力障碍）。组内发病率和流行率将按年龄、性别和种族/族裔估计。这将是第一次在种族和民族多样化的人群中对所有类型的PTD进行流行病学研究。第二个目的是通过验证的家族史访谈来调查病例和对照组中肌张力障碍的家族聚集性，并确定这种情况是否因肌张力障碍亚型和种族而异。第三个目标是确定与PTD相关的DYT1突变在由种族和临床特征定义的人群中的频率。目的4是研究环境暴露可能影响肌张力障碍表达和已知基因（DYT1）外显率的作用，包括特定的先前健康事件（创伤、感染）或生活方式因素（职业、爱好、吸烟、体育活动），通过比较这些事件在肌张力障碍发病前的频率，在病例和大约1000个匹配的对照中。这将是首次在大量未选择的多民族人群中调查PTD的发病率、流行率和相关危险因素。这将是流行病学上研究过的最大的PTD人群。该研究环境的优势包括：(1)人口学上与北加州的潜在人群相似；(2)获得护理的机会不受限制，减少了偏倚的确定；(3)可获得大量对照人群；(4)可以通过计算机记录识别某些与健康相关的风险因素，最大限度地减少了回忆偏倚。这些调查有可能为肌张力障碍的决定因素提供重要的见解。此外，该队列将为未来的研究提供丰富的资源，包括家庭研究、遗传分析和进一步的环境风险因素调查。

DESCRIPTION (provided by applicant): Dystonia is a disabling neurodegenerative disease that causes sustained involuntary muscle contractions, producing twisting, repetitive and patterned movements or abnormal postures. While it is the third most common movement disorder, little is known about ethnic or racial variation in the occurrence of dystonia or about risk factors. To address this problem, we will establish a dystonia incident cohort identified from among approximately 3 million individuals in a large, multiethnic (~40% non-white) health maintenance organization. We expect to identify at least 1000 incident cases of primary torsion dystonia (PTD). This will constitute by far the largest population of PTD patients ever enrolled in an epidemiologic study and will provide the foundation for addressing, for the first time, a number of questions regarding the epidemiology of dystonia. The first aim of this application is to estimate the incidence and prevalence of PTD overall and for clinically-defined subtypes (including generalized, cranial, cervical, limb and laryngeal dystonias). Incidence and prevalence within groups will be estimated by age, gender and race/ethnicity. This will be the first epidemiologic study of PTD of all types in a racially and ethnically diverse population. The second aim will be to investigate familial aggregation of dystonia in cases and controls, as measured by validated family history interviews, and to determine if this varies by subtype of dystonia and ethnicity. The third aim is to determine the frequency of the DYT1 mutation, associated with PTD, within groups defined by ethnicity and clinical features. Aim 4 is to investigate the role of environmental exposures that may influence the expression of dystonia and the penetrance of the known gene (DYT1), including specific antecedent health events (trauma, infection) or lifestyle factors (occupation, hobbies, cigarette smoking, physical activity) by comparing the frequency of these events before dystonia onset in cases and approximately 1000 matched controls. This will be the first investigation of the incidence, prevalence, and associated risk factors of PTD in-a large unselected multiethnic population. It will be the largest population of PTD ever studied epidemiologically. Advantages of the study setting include: (1) it is demographically similar to the underlying population of northern California, (2) access to care is unrestricted, reducing biased ascertainment, (3) a large control population is available and (4) certain health-related risk factors can be identified through computerized records, minimizing recall bias. These investigations have the potential to provide significant insights into the determinants of dystonia. In addition, this cohort will provide a rich resource for future investigations including family studies, genetic analyses and further investigations of environmental risk factors.