Cognitive Endophenotypes for Genetic Studies of Alzheimer's Disease

阿尔茨海默病遗传研究的认知内表型

• 批准号: 7907593
• 负责人: Kathleen M Hayden
• 金额: $ 11.95万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7907593
• 关键词: Academic Medical Centers; Address; Aging; Alzheimer' s Disease; Applications Grants; Area; Autopsy; Bioinformatics; Biometry; Clinic; Clinical; Clinical Data; Cognitive; Collection; Computational Biology; County; Data; Data Set; Detection; Development; Development Plans; Disease; Disease Pathway; Doctor of Philosophy; Elderly; Environment; Factor Analysis; Family; Family member; Funding; Future; Genes; Genetic; Genome; Genomics; Genotype; Goals; Heritability; Individual; Institutes; Learning; Longitudinal Studies; Memory; Mental Depression; Mentors; Methodology; Methods; Modeling; Neurocognitive; Neuropsychological Tests; Outcome; Participant; Pathology; Pattern; Performance; Pharmacogenetics; Population; Population Genetics; Predictive Value of Tests; Prospective Studies; Registries; Research; Research Design; Research Personnel; Resources; Risk; Risk Factors; Sampling; Science Policy; Testing; Training; Training Programs; Twin Multiple Birth; Twin Studies; United States National Institutes of Health; Veterans; Work; base; career development; clinical Diagnosis; clinical phenotype; cohort; data collection methodology; design; endophenotype; geriatric depression; neuropsychological; programs; therapy development

DESCRIPTION (provided by applicant): In this K01 application, Kathleen Hayden PhD is seeking training in genetics with a goal of exploring cognitive endophenotypes (latent or sub-clinical phenotypes representing the underlying disease genotype) of Alzheimer disease (AD) to inform ongoing and future genetic studies. The project builds on the candidate's prior work and is focused on providing advanced expertise in the area of genetics in order to facilitate her development as an independent researcher. The plan leverages the research environment and ample resources of the Bryan Alzheimer's Disease Research Center (Bryan ADRC) and its partners, the Duke Institute for Genome Sciences and Policy (IGSP), the Center for the Study of Aging, and the Department of Biostatistics and Bioinformatics. The research plan in this application is focused on advancing methodology to enhance the detection of yet to be determined risk genes involved in AD. This application proposes to use samples from four large NIH funded studies which have all been harmonized in their clinical data collection methodologies (Cache County Memory Study, Bryan ADRC cohorts, NAS-NRC Twin Study, and the Neurocognitive Outcomes of Depression in the Elderly Study) to rigorously determine AD endophenotypes using hypothesis driven and empirically based statistical approaches. Guided by Mentors, Kathleen Welsh-Bohmer (Bryan ADRC & CCMS PI) and David Goldstein (Director of Population Genomics & Pharmacogenetics IGSP) the candidate's career development plan will also benefit from the input of collaborators Carl Pieper (biostatistics), Brenda Plassman (twin studies), and David Steffens (geriatric depression) as she strives to understand and develop latent models within the unique cohorts: The training program includes coursework in latent class analysis, latent class trajectories, genetics, and computational biology as well as experiential training in neuropsychological methods, genetic study design, and statistical approaches unique to genetic methodologies. This relevant and timely application addresses a need to apply endophenotyping methods to population genetic work. Ultimately the application of endophenotypes of AD will facilitate the identification of new genes, highlight potential causal pathways of disease, and suggest avenues for future treatment development.

描述（由申请人提供）：在此K01应用中，凯瑟琳·海登（Kathleen Hayden）博士正在寻求遗传学培训，其目的是探索代表阿尔茨海默氏病（AD）的认知性内表型（代表基本疾病基因型的潜在或临床表型），以告知正在进行的和未来的遗传研究。该项目以候选人的先前工作为基础，并专注于在遗传学领域提供高级专业知识，以促进她作为独立研究人员的发展。该计划利用了布莱恩·阿尔茨海默氏病研究中心（Bryan ADRC）及其合作伙伴，杜克大学基因组科学与政策研究所（IGSP），衰老研究中心以及生物统计学和生物信息学系的研究环境和丰富资源。该应用程序中的研究计划的重点是推进方法，以增强对AD中涉及的尚未确定的风险基因的检测。该申请建议使用四项大型NIH资助的研究中的样本，这些样品在其临床数据收集方法中都得到了协调（Cache县记忆研究，Bryan ADRC同伴，NAS-NRC Twin研究和老年人研究中抑郁症的神经认知结果），以使用假设驱动的统计方法来确定严格的抑郁症的神经认知能力。 Guided by Mentors, Kathleen Welsh-Bohmer (Bryan ADRC & CCMS PI) and David Goldstein (Director of Population Genomics & Pharmacogenetics IGSP) the candidate's career development plan will also benefit from the input of collaborators Carl Pieper (biostatistics), Brenda Plassman (twin studies), and David Steffens (geriatric depression) as she strives to understand and develop latent models within独特的人群：培训计划包括潜在类别分析，潜在类轨迹，遗传学和计算生物学的课程以及神经心理学方法中的经验培训，遗传研究设计以及遗传学方法独有的统计方法。这种相关和及时的应用程序解决了将内聚型方法应用于人群遗传工作的需求。最终，AD内表型的应用将促进新基因的鉴定，突出潜在的疾病因果途径，并为未来的治疗发展提供途径。