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

阿尔茨海默病遗传学和基因组学协调中心 (CGAD)

• 批准号: 9472453
• 负责人: GERARD DAVID SCHELLENBERG
• 金额: $ 25.76万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2020-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9472453
• 关键词: Affect; African American; Alzheimer' s Disease; Asians; Biometry; Caribbean Hispanic; Collaborations; Cost of Illness; Data; Data Analyses; Data Set; Databases; Deposition; Detection; Disease; Disease Progression; Ensure; Ethnic group; European; Family; Funding; Gene Targeting; Genes; Genetic; Genetic Research; Genetic study; Genomics; Genotype; Goals; Grant; Hereditary Disease; Knowledge; Meta-Analysis; National Institute on Aging; Nucleotides; Pathway Analysis; Pathway interactions; Phase; Process; Protocols documentation; Quality Control; Research Personnel; Risk; Site; Source; Testing; Therapeutic; Time; Variant; base; case control; cost; data management; database of Genotypes and Phenotypes; design; exome; gene discovery; genetic variant; insertion/deletion mutation; insight; phenotypic data; prevent; public health relevance; therapeutic target; whole genome

 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.

 描述（由申请人提供）：阿尔茨海默病（AD）遗传学研究的目标是确定导致、影响风险或预防这种疾病的遗传变异，并确定受这些变异影响的潜在基因。这些基因是潜在的治疗靶点。NIA阿尔茨海默病遗传学和基因组学协调中心（CGAD，本申请）的目标是通过协调所有AD相关数据的分析来促进AD基因的发现。根据RFA AG16001的规定，有3个核心和一个整体组件。规定的核心是：1）行政（核心A）; 2）数据管理、协调和信息传输核心（核心B）; 3）生物统计和数据分析核心（核心C）。根据RFA AG16001的要求，CGAD将收集阿尔茨海默病序列项目（ADSP）在发现阶段和复制阶段生成的所有数据（核心A和B），以及来自非ADSP来源的所有数据（核心A），包括RFA AG16002资助的赠款生成的数据。CGAD将; 1）创建并支持所有CGAD、ADSP、RFA AG16002和其他AD遗传学研究者的协作网络（核心A）; 2）协调所有遗传和表型数据并完整注释所有变体（核心B）; 2）设计所有协调和注释方案（核心C，由核心B实施）; 3）为所有数据设计分析方案（核心C）; 4）实施分析计划（核心C，除了将由核心B执行的计算密集型协议）; 5）广泛分发原始数据、统一的注释分析就绪文件，并分析结果，包括将适当的数据存入合格的访问数据库[国家老年痴呆症遗传学研究所存储站点（NIAGADS）和基因型和表型数据库（dbGaP）]（核心B）。根据RFA AG16001的要求，将与所有ADSP、RFA AG16002和其他AD遗传学研究者合作，完善所有协调方案和分析计划。总体构成部分详细说明了拟由各核心执行的活动和分析。我们将使用单个和基于基因的分析来分析复制阶段数据。将分析单核苷酸变体（SNV）和结构变体（SV）。我们将对复制阶段和发现阶段数据进行综合分析。我们还将使用非ADSP数据执行扩展复制阶段。我们将分析来自通路网络分析、相互作用分析和多基因风险评分中所有阶段的数据。这些基因发现活动将为开发治疗药物带来潜在的靶点。