Translational phenomics and genomics of Gilles de la Tourette Syndrome

Gilles de la Tourette综合征(GTS)是一种常见的、高度遗传性的儿童期起病的神经精神病学 以显著的临床异质性和对现有治疗的不同反应为特征的一种障碍。 这个以患者为中心的研究(K23)的指导职业发展奖的目的是培训 统计学、遗传学和临床流行病学方法的候选人，这样他就可以成为一个独立的 转化型、临床遗传学研究的研究员。研究计划包括：1)临床 表型目的用项目水平的探索性和验证性因素分析来定义同质性， 基于症状的GTS“亚型”，可能更充分地反映了GTS的不同临床特征 疾病；2)GTS全基因组关联研究(GWAS)的二次分析 目标1中用于识别GTS易感等位基因的亚表型；3)候选人将 参与他的合作导师试点的选定方面，组合行为的随机对照试验 GTS的治疗和药物治疗，以获得进行未来GTS所需的技能和经验 可以结合治疗反应的表型和遗传预测因子的临床试验。‘ 这项拟议的研究将在马萨诸塞州综合医院进行，由大卫指导 Pauls博士，GTS表型和基因研究专家，Sabine Wilhelm的共同导师， 博士，GTS治疗研究方面的专家。一群全国公认的导师和顾问，都是 本地的和外部的，将在与每个相关的专业领域提供额外的指导 研究和培训目标。职业发展计划包括一个说教部分，结合 哈佛大学公共卫生学院和哈佛大学心理学系的课程 研究设计、生物统计学、统计遗传学和临床TALS方法的指导教程。这一集成 研究和培训计划将为未来的多中心药物遗传学研究奠定基础 GTS治疗反应，并将准备候选人提交R01翻译遗传申请 GTS及相关疾病的研究。 相关性(请参阅说明)： 这项研究旨在为GTS定义更精确的疾病定义，识别GTS易感基因， 并对研究人员进行临床试验方法方面的培训，以便他能够应用这些新的疾病定义和 基因对未来GTS治疗研究的影响。这项研究的完成将培养调查员成为领导者 旨在为GTS患者开发个性化治疗的转化性研究。

Gilles de la Tourette Syndrome (GTS) is a common, highly heritable, childhood-onset neuropsychiatric disorder that is characterized by marked clinical heterogeneity and variable response to existing treatments. The purpose of this Mentored Career Development Award in Patient-Oriented Research (K23) is to train the candidate in statistical, genetic and clinical epidemiologic methods so that he can become an independent investigator in translational, clinical genetic research. The research plan consists of: 1) a clinical phenotyping aim using item-level exploratory and confirmatory factor analysis to define homogeneous, symptom-based GTS "subphenotypes" that may more adequately capture the diverse clinical features of the disease; 2) a secondary analysis of a GTS genome-wide association study (GWAS) using the heritiable subphenotypes in Aim 1 to identify GTS susceptibility alleles; 3) a training aim in which the candidate will participate in selected aspects of his co-mentor's pilot, randomized controlled trial of combined behavioral therapy and pharmacotherapy for GTS to acquire the skills and experience necessary to conduct future GTS clinical trials that can incorporate phenotypic and genetic predictors of treatment response. ' The proposed study will be conducted at Massachusetts General Hospital under the mentorship of David Pauls, Ph.D., an expert in GTS phenotypic and genetic research, and the co-mentorship of Sabine Wilhelm, Ph.D., an expert in GTS treatment research. A group of nationally-recognized mentors and consultants, both local and external, will provide additional mentoring in specialized areas of expertise relevant to each research and training goal. The career development plan includes a didactic component combining coursework at the Harvard School of Public Health and Harvard University Department of Psychology with guided tutorials in study design, biostatistics, statistical genetics, and clinical thals methods. This integrated research and training program will lay the groundwork for future, multi-center pharmacogenetic studies of GTS treatment response and will prepare the candidate to submit an R01 application for translational genetic studies of GTS and related disorders. RELEVANCE (See instructions): This research aims to define more precise disease definitions for GTS, to identify GTS susceptibility genes, and to train the investigator in clinical trials methods so that he can apply these novel disease definitions and genes to future GTS treatment studies. Completion of this study will train the investigator to become a leader in translational research aimed at developing personalized treatments for GTS patients.