Epidemiology of Dystonia in a Multi-Ethnic Population

描述(申请人提供)：肌张力障碍是一种致残的神经退行性疾病，导致持续的非自愿肌肉收缩，产生扭曲、重复和有图案的运动或异常姿势。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种族或种族差异或危险因素知之甚少。为了解决这个问题，我们将建立一个肌张力障碍事件队列，从一个大型多种族(约40%非白人)健康维护组织的大约300万人中确定。我们预计将确认至少1000例原发性扭转肌张力障碍(PTD)的事件。这将构成迄今为止参加流行病学研究的PTD患者人数最多的一次，并将为首次解决有关肌张力障碍的流行病学问题奠定基础。这项应用的第一个目标是评估PTD的总体发病率和患病率，以及临床定义的亚型(包括全身型、颅型、颈型、四肢型和喉型)。将按年龄、性别和种族/族裔估计群体内的发病率和流行率。这将是第一次在种族和民族多样化的人群中进行所有类型PTD的流行病学研究。第二个目标是调查病例和对照中肌张力障碍的家族聚集性，通过有效的家族史访谈来衡量，并确定这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群体中的频率。目的4研究环境暴露对肌张力障碍的表达和已知基因(DYT1)外显性的影响，包括特定的既往健康事件(创伤、感染)或生活方式因素(职业、爱好、吸烟、体力活动)，通过比较病例和大约1000名匹配的对照组肌张力障碍发作前这些事件的频率，来研究环境暴露的作用。这将是第一次对PTD的发病率、患病率和相关危险因素进行调查--在大量未经选择的多民族人群中。这将是流行病学研究中PTD人数最多的一次。研究环境的优点包括：(1)在人口统计学上与加利福尼亚州北部的潜在人口相似；(2)获得护理的机会不受限制，减少了有偏见的确定；(3)有大量的对照人群；(4)某些与健康相关的风险因素可以通过计算机化的记录识别，最大限度地减少回忆偏差。这些研究有可能为肌张力障碍的决定因素提供重要的见解。此外，这一队列将为未来的调查提供丰富的资源，包括家庭研究、遗传分析和进一步调查环境风险因素。

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.