Translational phenomics and genomics of Gilles de la Tourette Syndrome

Gilles de la Tourette 综合征的转化表型组学和基因组学

• 批准号: 7904051
• 负责人: Jeremiah M Scharf
• 金额: $ 18.58万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7904051
• 关键词: Adult; Alleles; Area; Behavior Therapy; Biometry; Characteristics; Childhood; Classification; Clinical; Clinical Research; Clinical Trials; Data; Data Analyses; Development Plans; Diagnostic; Disease; Doctor of Philosophy; Double-Blind Method; Epidemiologic Methods; Factor Analysis; Future; General Hospitals; Genes; Genetic; Genetic Heterogeneity; Genetic Research; Genomics; Gilles de la Tourette syndrome; Goals; Guanfacine; Habits; Heterogeneity; Individual; Instruction; K-Series Research Career Programs; Knowledge; Laboratories; Lead; Learning; Massachusetts; Mentors; Mentorship; Methods; Modeling; Morbidity - disease rate; Multi-Institutional Clinical Trial; Patients; Pharmacogenetics; Pharmacotherapy; Phenotype; Pilot Projects; Placebos; Positioning Attribute; Predisposition; Psychology; Public Health Schools; Randomized Controlled Trials; Research; Research Design; Research Personnel; Research Training; Sampling; Selection for Treatments; Single Nucleotide Polymorphism; Statistical Methods; Susceptibility Gene; Symptoms; System; Techniques; Training; Training Programs; Translational Research; Universities; Variant; base; career; career development; clinical phenotype; design; disability; discrete data; effective therapy; experience; genome wide association study; investigator training; neuropsychiatry; novel; patient oriented research; phenomics; psychosocial; response; skills; treatment response

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：抽动秽语综合征（GTS）是一种常见的、高度遗传的、儿童期发作的神经精神疾病，其特征是显著的临床异质性和对现有治疗的可变反应。这项以患者为导向的研究（K23）指导职业发展奖的目的是对候选人进行统计、遗传和临床流行病学方法的培训，以便他能够成为转化、临床遗传研究的独立研究者。研究计划包括：1）临床表型目标，其使用项目水平探索性和验证性因素分析来定义同质的、基于GTS的“亚表型”，其可以更充分地捕获疾病的不同临床特征; 2）GTS全基因组关联研究（GWAS）的二次分析，其使用目标1中的可遗传亚表型来鉴定GTS易感性等位基因; 3）培训目标，其中候选人将参加其共同导师的试点，GTS的行为疗法和药物疗法联合随机对照试验的选定方面，以获得进行未来GTS临床试验所需的技能和经验，这些临床试验可以结合治疗反应的表型和遗传预测因子。“拟议的研究将在马萨诸塞州总医院进行，由大卫保罗博士指导，GTS表型和遗传研究专家，以及Sabine Wilhelm博士的共同指导，GTS治疗研究专家。一组国家承认的本地和外部导师和顾问将在与每一项研究和培训目标有关的专门知识领域提供更多的辅导。职业发展计划包括一个教学部分，将哈佛公共卫生学院和哈佛大学心理学系的课程与研究设计、生物统计学、统计遗传学和临床治疗方法的指导教程相结合。该综合研究和培训计划将为未来GTS治疗反应的多中心药物遗传学研究奠定基础，并为候选人提交GTS和相关疾病转化遗传学研究的R 01申请做好准备。相关性（参见说明）：本研究旨在为GTS定义更精确的疾病定义，识别GTS易感基因，并培训研究者临床试验方法，以便他可以将这些新的疾病定义和基因应用于未来的GTS治疗研究。本研究的完成将培养研究者成为旨在为GTS患者开发个性化治疗的转化研究的领导者。