Harmonization of Additional Data Sets for the Alzheimer's Disease Sequencing Project (ADSP) Follow-Up Study (FUS)

阿尔茨海默病测序项目 (ADSP) 后续研究 (FUS) 附加数据集的协调

• 批准号: 10184590
• 负责人: Margaret A. Pericak-Vance
• 金额: $ 37万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10184590
• 关键词: Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer' s disease therapy; Aspirin; Cohort Analysis; Cohort Studies; Communities; Data; Data Collection; Data Set; Dementia; Diagnostic; Elderly; Environment; Ethnic group; Event; Family Study; Follow-Up Studies; Funding; Future; Genes; Genetic; Genetic Variation; Goals; India; Infrastructure; Knowledge; Large-Scale Sequencing; Life; Longitudinal Studies; Phenotype; Population; Predisposition; Procedures; Quality Control; Race; Research; Research Personnel; Resources; Source; Speed; clinical phenotype; clinically relevant; cohort; data harmonization; design; gene discovery; genetic variant; genomic locus; phenotypic data

ABSTRACT Alzheimer disease (AD) is the leading cause of dementia in older adults and occurs in all ethnic and racial groups. A multitude of studies have identified multiple AD associated genes and loci, but a large portion of the genetic contribution to AD remain unknown. The Alzheimer Disease Sequencing Project (ADSP) is using large-scale sequencing efforts to increase our knowledge about the genetic variation that influences AD, particularly rare genetic variants that enhance AD risk or protect against AD. A major initiative within the ADSP is the Follow Up Study (ADSP-FUS), an expansion of gene discovery efforts to include diverse and unique population. Over the past 12 months, the scope of the ADSP-FUS has expanded to include a number of new cohorts for sequencing. The inclusion of these new cohorts, which have a broad span of clinical-phenotype information, significantly enriches the value of the ADSP in achieving its goal of increasing knowledge of genetic variation in AD across different populations. This supplement is designed to complete pre-statistical harmonization activities in six new cohorts that will be included in the larger harmonization of clinical-phenotype data in all of the ADSP datasets. The final ADSP harmonized dataset, which includes all cohorts (and future cohorts) will create an invaluable, much needed, legacy resource for the NIA. We will perform comprehensive pre-harmonization activities for the six new FUS cohorts (Age, Gene/Environment Susceptibility (AGES) Study; Longitudinal Study of Aging in India-Diagnostic Assessment of Dementia (LASI-DAD); Gwangju Alzheimer and Related Dementias (GARD) Study; Long Life Family Study (LLFS); Aspirin in Reducing Events in the Elderly (ASPREE) Trial Cohort; Iberian Peninsula Cohort) that are not currently funded through other sources. Given that these cohorts vary in their focus (i.e., not all are dementia cohorts) there is a wide span of clinical-phenotype information which makes harmonization challenging. Creating a pre-statistical harmonization workflow in which these data are prepared and used by the ADSP-Harmonization Consortium will expedite the delivery of harmonized clinical-phenotype data to the larger AD community. To complete the pre-statistical harmonization efforts, we will: (a) Identify, collect and organize clinical-phenotype data from the new cohorts, (b) Review and document procedures for data collection for all relevant clinical-phenotype variables, and (c) Perform preliminary quality control analyses for cohort specific data. The successful completion of the proposed pre-statistical harmonization will yield harmonization ready data for the six cohorts that will be utilized in the statistical harmonization of all ADSP datasets. Just as important, this supplement will establish an infrastructure for implementing pre-statistical harmonization that will be integrated into the ADSP-Harmonization Consortium. In the long run, by enhancing harmonization of the ADSP cohorts we are helping make available valuable sequence data to the AD research community to speed gene discovery and identify targets for AD therapies.

抽象的 阿尔茨海默氏病（AD）是老年人痴呆症的主要原因，发生在所有种族和种族群体中。 大量研究已经鉴定了多个AD相关的基因和基因座，但是很大一部分遗传 对广告的贡献仍然未知。阿尔茨海默氏病测序项目（ADSP）正在使用大规模 测序努力以增加我们对影响AD的遗传变异的了解，尤其是罕见 增强AD风险或防止AD的遗传变异。 ADSP中的主要倡议是后续行动 研究（ADSP-FUS），这是基因发现的扩展，以包括不同和独特的人群。在 在过去的12个月中，ADSP-FUS的范围已扩大到包括许多新的同类群体进行测序。 包括这些新队列的临床表型信息，包括这些新队列 丰富ADSP的价值在实现其增加对AD遗传变异知识的目标方面的目标 不同的人群。 该补充旨在完成六个新同龄人的统计前协调活动，这将是 包括在所有ADSP数据集中临床 - 表型数据的较大协调中。最终ADSP 包括所有队列（和未来人群）的协调数据集将创建一个无价的，急需的，非常需要的， NIA的遗产资源。我们将为六个新的FUS进行全面的戒酒前活动 队列（年龄，基因/环境易感性（年龄）研究；印度诊断衰老的纵向研究 评估痴呆症（Lasi-dad）； Gwangju Alzheimer和相关痴呆症（GARD）研究；长寿 家庭研究（LLFS）；阿司匹林减少老年人（Aspree）试验队列中的事件；伊比利亚半岛队列） 目前尚未通过其他来源资助。鉴于这些队列的重点有所不同（即，并非所有人都 痴呆群体）有广泛的临床表型信息，这使得协调一致 具有挑战性的。创建统计前的协调工作流程，在其中准备和使用这些数据 Adsp-Harmonization Consortium将加快统一的临床表型数据的速度向较大的数据传递 广告社区。为了完成统计前的协调工作，我们将：（a）确定，收集和组织 来自新队列的临床表型数据，（b）所有人的数据收集的审查和文档程序 相关的临床表型变量，（c）对比特特异性进行初步质量控制分析 数据。 提议的统计前协调的成功完成将产生准备就绪数据 将在所有ADSP数据集的统计协调中使用的六个队列。同样重要的是 补充将建立一个基础架构，用于实施统计前协调 进入Adsp-Harmonation Consortium。从长远来看，通过增强ADSP队列的协调我们 正在帮助向广告研究社区提供有价值的序列数据，以加快基因发现和 确定广告疗法的靶标。