Cognitive Endophenotypes for Genetic Studies of Alzheimer's Disease

描述（由申请人提供）：在此K 01申请中，Kathleen Hayden博士正在寻求遗传学培训，目的是探索阿尔茨海默病（AD）的认知内表型（代表潜在疾病基因型的潜在或亚临床表型），以告知正在进行和未来的遗传学研究。该项目建立在候选人以前的工作基础上，重点是提供遗传学领域的先进专业知识，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病研究中心（Bryan ADRC）及其合作伙伴，杜克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充足的资源。本申请中的研究计划侧重于推进方法学，以增强对涉及AD的尚未确定的风险基因的检测。本申请提出使用来自四项大型NIH资助研究的样本，这些研究在其临床数据收集方法（Cache County Memory Study、Bryan ADRC cohort、NAS-NRC Twin Study和Neurocognitive Outcomes of Depression in the Elderly Study）中均已协调，以使用假设驱动和基于经验的统计方法严格确定AD内表型。导师：Kathleen Welsh-Bohmer（Bryan ADRC & CCMS PI）和大卫戈尔茨坦（人口基因组学和药物遗传学IGSP主任）候选人的职业发展计划也将受益于合作者卡尔皮珀的投入（生物统计学），布伦达·普拉斯曼（双胞胎研究），和大卫斯蒂芬斯（老年抑郁症），因为她努力了解和开发独特的队列内的潜在模型：培训计划包括潜在类分析，潜在类轨迹，遗传学和计算生物学课程，以及神经心理学方法，遗传研究设计和遗传方法特有的统计方法的经验培训。这种相关和及时的应用解决了将内表型分析方法应用于群体遗传学工作的需要。最终，AD内表型的应用将有助于识别新基因，突出疾病的潜在因果途径，并为未来的治疗开发提供途径。

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.