Planning grant: Columbia-Yale-Bilkent Study: Genetic Study of Essential Tremor

描述：这是一份研究发展/规划拨款申请，旨在启动合作研究 与土耳其比尔肯特大学的研究人员一起研究本质震颤的遗传学。本质震颤 (ET)是最常见的神经系统疾病之一，估计有700万人在 美国。ET最典型的临床特征是手部或手臂的运动性震颤， 在疾病过程的早期是轻微的。随着病情的发展，震颤变得越来越严重。 在解剖学上广泛分布(例如，头部、躯干)。除了震颤，ET患者还可能出现其他 运动特征包括步态共济失调。非运动特征可包括精神症状、认知功能 衰老和痴呆症。尽管ET的患病率非常高，但其遗传原因主要是 未知。我们建议开展一项针对土耳其血缘家庭的ET遗传学研究。 土耳其约有7000万人口，近亲结婚率很高。这一速度 血缘关系估计高达20%-25%，约占所有血缘关系的70% 有近亲关系的婚姻。在土耳其人群中研究ET的遗传学，特别是在大范围内 有血缘关系的家系可能会发现与ET人群相关的新的ET遗传原因 美国和世界各地。建议的研究与我们的合作者DRS有很高的成功几率 Ozcelik和Tekinay在人类遗传学和功能研究方面的专业知识，以及 有血缘关系的ET大家族的资源。这笔规划拨款的具体目的是：(1)进一步 发展和巩固与比尔肯特团队的合作，并确定研究的范围 R01应用程序的重点；(2)评估Bilkent团队的资源和需求，以便成功 开展研究；(3)在以下领域实施美国和土耳其团体的交叉培训 人类遗传学、遗传流行病学和风险因素评估、基因组学、临床诊断、功能 研究和个性化基因组医学；以及(4)进行试点研究以产生初步数据 对于R01应用程序来说是必需的。

DESCRIPTION: This is a research development/planning grant application to initiate collaborative studies with investigators at Bilkent University in Turkey to study the genetics of Essential Tremor. Essential Tremor (ET) is one of the most common neurological diseases, with an estimated 7 million affected individuals in the United States. The most characteristic clinical feature of ET is a kinetic tremor in the hands or arms, which early in the disease process is mild. As the disease progresses, tremor becomes more severe and more anatomically widespread (e.g., head, trunk). Aside from tremor, patients with ET may also present with other motor features including gait ataxia. Non-motor features can include psychiatric manifestations, cognitive decline and dementia. Despite its extraordinarily high prevalence the genetic causes of ET are largely unknown. We propose to develop a genetic study of ET focusing on consanguineous families in Turkey. Turkey with a population of about 70 million has a high rate of consanguineous marriages. The rate of consanguinity is estimated to be as much as 20-25% with approximately 70% of all consanguineous marriages involving first cousins. Studying the genetics of ET in the Turkish population, particularly in large consanguineous families may identify novel genetic causes of ET that are also relevant to ET populations in the US and worldwide. The proposed research has a high probability of success with our collaborators, Drs Ozcelik and Tekinay's expertise in human genetics and functional studies together with an established resource of large consanguineous ET families. The specific aims of this planning grant are to: (1) further develop and solidify collaborations with the team in Bilkent and define the scope of the research that will be the focus of an R01 application; (2) assess the Bilkent team's resources and needs in order to successfully conduct the research; (3) implement cross-training between the U.S. and Turkish groups in the areas of human genetics, genetic epidemiology and risk factor assessment, genomics, clinical diagnosis, functional studies and personalized genomic medicine; and (4) conduct pilot studies to generate preliminary data necessary for an R01 application.