Coordinating Center for Genetics and Genomics of Alzheimer's Disease (CGAD)

 描述(申请人提供)：阿尔茨海默病(AD)遗传学研究的目标是识别导致、影响风险或预防这种疾病的遗传变异，并识别受这些变异影响的潜在基因。然后，这些基因就成为潜在的治疗靶点。NIA阿尔茨海默病遗传学和基因组学协调中心(CGAD)的目标是通过协调分析所有与AD相关的数据来促进AD基因的发现。按照RFA AG16001的要求，有3个核心和一个整体组件。授权的核心是：1)行政(核心A)；2)数据管理、协调和信息传输核心(核心B)；以及3)生物统计和数据分析核心(核心C)。根据RFA AG16001的要求，CGAD将汇集阿尔茨海默病序列项目(ADSP)从发现阶段和复制阶段产生的所有数据(核心A和B)，以及来自非ADSP来源(核心A)的所有数据，包括由RFA AG16002资助的赠款产生的数据。CGAD将；1)创建和支持所有CGAD、ADSP、RFA AG16002和其他AD遗传学调查人员的协作网络(核心A)；2)协调所有遗传和表型数据，并对所有变异进行充分注释(核心B)；2)设计所有协调和注释协议(核心C，由核心B执行)；3)设计所有数据的分析协议(核心C)；4)实施分析计划(核心C，计算密集型协议除外，将由核心B执行)；5)广泛分发原始数据，统一加注释的分析文件，并分析结果，包括将适当的数据存入合格的Access数据库[阿尔茨海默病国家老龄遗传学研究所(NIAGADS)和基因类型和表型数据库(DBGaP)](核心B)。根据RFA AG16001的授权，所有协调方案和分析计划将与所有ADSP、RFA AG16002和其他AD遗传学调查人员合作进行完善。总体构成部分详细说明了拟由各核心执行的活动和分析。我们将使用单一分析和基于基因的分析来分析复制阶段数据。单核苷酸变异(SNV)和结构变异(SVS)都将被分析。我们将对复制和发现阶段数据执行综合分析。我们还将使用非ADSP数据执行扩展复制阶段。我们将在通路网络分析、相互作用分析和多基因风险评分中分析所有阶段的数据。这些基因发现活动将成为开发治疗药物的潜在目标。

 DESCRIPTION (provided by applicant): The goal of Alzheimer's disease (AD) genetics research is to identify genetic variants that cause, influence risk, or protect against this disordr, and to identify the underlying genes affected by these variants. These genes are then potential therapeutic targets. The goal of the NIA Coordinating Center for Genetics and Genomics of Alzheimer's Disease (CGAD, this application) is to facilitate AD gene discovery by coordinating analysis of all AD-relevant data. As mandated by RFA AG16001, there are 3 cores and an Overall Component. The mandated cores are: 1) Administrative (Core A); 2) Data Management, Harmonization, and Information Transfer Core (Core B); and 3) Biostatistics and Data Analysis Core (Core C). As mandated by RFA AG16001, CGAD will assemble all data (Cores A and B) generated by the Alzheimer's Disease Sequence Project (ADSP) from both the Discovery Phase and the Replication Phase, and all data from non-ADSP sources (Core A) including that generated by grants funded under RFA AG16002. CGAD will; 1) create and support a collaborative network of all CGAD, ADSP, RFA AG16002, and other AD genetics investigators (Core A); 2) harmonize all genetic and phenotype data and fully annotate all variants (Core B); 2) design all harmonization and annotation protocols (Core C, implemented by Core B); 3) design analysis protocols for all data (Core C); 4) implement analyses plans (Core C, except for computationally intensive protocols that will be executed by Core B); 5) broadly distribute primary data, harmonized annotated analysis-ready files, and analyses results including depositing appropriate data into qualified access databases [National Institute on Aging Genetics of Alzheimer's Disease Storage site (NIAGADS) and database of Genotypes and Phenotypes (dbGaP)] (Core B). As mandated by RFA AG16001, all harmonization protocols and analyses plans will be refined in collaboration with all ADSP, RFA AG16002, and other AD genetics investigators. The Overall Component describes in detail the proposed activities and analyses to be executed by the cores. We will analyze Replication Phase data using single and gene-based analyses. Both single nucleotide variants (SNVs) and structural variants (SVs) will be analyzed. We will perform a combined analysis of Replication and Discovery Phase data. We will also perform an Extended Replication Phase using non- ADSP data. We will analyze data from all phases in a pathway network analysis, an interaction analysis, and a polygenic risk score. These gene-discovery activities will lead to potential targets for developing therapeutics.