Genetic architecture of memory and executive functioning in Alzheimer's disease

阿尔茨海默病记忆和执行功能的遗传结构

• 批准号: 8630958
• 负责人: Paul K Crane
• 金额: $ 76.78万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8630958
• 关键词: Abbreviations; Accounting; Adult; Aging; Alzheimer' s Disease; Architecture; Candidate Disease Gene; Clinical; Clinical Data; Cognition; Cognitive; Cohort Studies; Data; Data Set; Detection; Development; Diabetes Mellitus; Diagnosis; Disease; Elderly; Epidemiology; Executive Dysfunction; Funding Mechanisms; Genes; Genetic; Genetic Variation; Genome; Genotype; Goals; Height; Heritability; Hypertension; Investigation; Knowledge; Late Onset Alzheimer Disease; Lead; Memory; Methods; Metric; Names; Nucleotides; Parents; Participant; Pathway interactions; Pattern; Performance; Pharmaceutical Preparations; Phenotype; Prospective Studies; Psychometrics; Randomized; Relative (related person); Religion and Spirituality; Research; Research Personnel; Risk; Risk Factors; Series; Text; Time; Variant; Washington; Work; clinical epidemiology; disorder subtype; drug development; executive function; exome; exome sequencing; family structure; genetic analysis; genetic risk factor; genome sequencing; genome-wide; improved; neuropsychological; prospective; public health relevance; spelling

Ten to 25% of people with late-onset Alzheimer's disease (AD) present with prominent executive deficits. Names such as frontal variant AD, executive prominent AD, and dysexecutive AD have been applied to this phenomenon. Little is known about traditional or genetic risk factors for dysexecutive AD. The overarching goal of this project is to further our understanding of the genetic architecture and clinical epidemiology of dysexecutive AD in the hopes of ultimately developing disease- modifying treatments. This project will leverage large-scale genome-wide genotype and sequence data and cognitive data collected on >17,000 participants across 19 collaborating studies. The investigators will use modern psychometric methods to co-calibrate cognitive data to develop scores on the same metric for memory and executive functioning. The investigators will use these scores to determine a continuous dysexecutive spectrum phenotype they have found to be highly heritable, with a pattern of heritability entirely distinct from that of AD. The investigators will leverage genome-wide genotype data for Aim 1. Five of the collaborating studies are prospective cohort studies with extensive cognitive and clinical data from >10,000 participants. The investigators will leverage these data for Aim 2. Several funding mechanisms are producing whole genome and whole exome sequencing data for people with AD. The investigators will leverage these data for Aim 3. Taken together, these investigations promise to improve what is known about dysexecutive AD, a highly heritable and devastating AD subtype. This work may identify genetic loci associated with risk for dysexecutive AD, which in turn may lead to development of drugs that could dramatically improve the lives of people with this condition.

患有晚期阿尔茨海默氏病（AD）的人中有10％至25％的人出现了 执行赤字。诸如Frontal变体广告，执行著名广告和等名称 DySexecectectect已应用于此现象。对 DySexexecectAD的传统或遗传危险因素。总体目标 项目是为了进一步了解遗传结构和临床 DySexexection AD的流行病学，希望最终发展疾病 - 修改治疗。 该项目将利用大规模全基因组基因型和序列数据以及 在19个合作研究中收集了> 17,000名参与者的认知数据。这 研究人员将使用现代心理测量方法将认知数据共同核算 在同一指标上开发分数，以进行内存和执行功能。这 研究人员将使用这些分数来确定连续的DySexecectect频谱 他们发现的表型高度遗传，完全具有遗传力 与广告不同。调查人员将利用全基因组基因型数据 目标1。五项合作研究是前瞻性研究 来自> 10,000名参与者的认知和临床数据。调查人员将利用 这些针对AIM 2的数据。几种资金机制正在产生整个基因组和 为AD患者提供整个外显子组测序数据。调查人员将利用这些 AIM 3的数据。 综上所述，这些调查有望改善有关的事物 DySexexection AD，高度可遗传的毁灭性广告子类型。这项工作可以确定 遗传基因座与DySexectection AD的风险相关，这又可能导致 毒品的开发可以极大地改善人们的生活 健康）状况。