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

摘要 阿尔茨海默病（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种AD相关基因和位点，但大部分遗传学特征不完全一致。 对AD的贡献仍然未知。阿尔茨海默病测序项目（ADSP）正在使用大规模的 测序工作，以增加我们对影响AD的遗传变异的知识，特别是罕见的 遗传变异增加AD风险或预防AD。ADSP内部的一项主要举措是后续行动 研究（ADSP-FUS），基因发现工作的扩展，包括多样化和独特的人群。来 在过去的12个月里，ADSP-FUS的范围已经扩大到包括一些新的测序队列。 这些新的队列具有广泛的临床表型信息， 丰富了ADSP的价值，以实现其增加对AD遗传变异的了解的目标。 不同的人群。 该补编旨在完成六个新群组的统计前统一活动， 包括在所有ADSP数据集中的临床表型数据的更大协调中。最终ADSP 统一的数据集，其中包括所有队列（和未来的队列）将创建一个宝贵的，急需的， NIA的传统资源。我们将为六个新的FUS进行全面的协调前活动 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 家族研究（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） 目前没有其他来源的资金。考虑到这些群体的重点不同（即，不是所有人都 痴呆队列）存在广泛的临床表型信息， 挑战性建立一个统计前统一工作流程， ADSP-Harmonization Consortium将加快向更大的组织提供协调的临床表型数据。 AD社区为完成统计前的统一工作，我们将： 新队列的临床表型数据，（B）审查并记录所有数据收集程序 相关的临床表型变量，和（c）进行初步的质量控制分析， 数据 成功完成拟议的统计前统一工作将产生可供统一的数据， 将用于所有ADSP数据集的统计协调的六个群组。同样重要的是， 补编将为执行统计前统一建立基础设施， 加入ADSP协调联盟从长远来看，通过加强ADSP队列的协调， 正在帮助AD研究界获得有价值的序列数据，以加速基因发现， 确定AD治疗的靶点。

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.