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 阿尔茨海默病（AD）是老年人痴呆的主要原因，发生在所有民族和种族群体中。 大量研究已经确定了多个 AD 相关基因和位点，但大部分遗传 对 AD 的贡献仍然未知。阿尔茨海默病测序项目 (ADSP) 正在使用大规模 测序工作以增加我们对影响 AD 的遗传变异（尤其是罕见的）的了解 增加 AD 风险或预防 AD 的基因变异。 ADSP 的一项主要举措是后续行动 研究（ADSP-FUS）是基因发现工作的扩展，将多样化和独特的人群纳入其中。超过 过去 12 个月，ADSP-FUS 的范围已扩大到包括许多新的测序队列。 这些具有广泛临床表型信息的新队列的纳入，显着 丰富了 ADSP 在实现其目标方面的价值，即增加对 AD 遗传变异的了解 不同的人群。 该补充材料旨在完成六个新队列的统计前协调活动，这些新队列将被 包括在所有 ADSP 数据集中临床表型数据的更大协调中。最终的ADSP 统一的数据集，其中包括所有队列（以及未来的队列）将创建一个非常宝贵的、急需的、 NIA 的遗留资源。我们将为六个新的 FUS 开展全面的预协调活动 队列（年龄、基因/环境易感性（AGES）研究；印度老龄化纵向研究-诊断 痴呆症评估（LASI-DAD）；光州阿尔茨海默病和相关痴呆症（GARD）研究；长寿 家庭研究（LLFS）；阿司匹林减少老年人事件 (ASPREE) 试验队列；伊比利亚半岛队列） 目前尚未通过其他来源资助。鉴于这些群体的关注点各不相同（即并非所有群体都关注 痴呆队列）有广泛的临床表型信息，这使得协调一致 具有挑战性的。创建统计前协调工作流程，其中这些数据由 ADSP-协调联盟将加快向更大范围提供协调一致的临床表型数据 广告社区。为了完成统计前的协调工作，我们将： (a) 识别、收集和组织 来自新队列的临床表型数据，(b) 审查并记录所有人的数据收集程序 相关的临床表型变量，以及 (c) 对特定队列进行初步质量控制分析 数据。 成功完成拟议的统计前协调将为以下方面提供协调就绪的数据： 将用于所有 ADSP 数据集统计协调的六个队列。同样重要的是，这 补充文件将建立一个基础设施，用于实施统计前的统一，并将 加入 ADSP 协调联盟。从长远来看，通过加强 ADSP 群体的协调，我们 正在帮助向 AD 研究界提供有价值的序列数据，以加快基因发现和 确定 AD 治疗的靶标。