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。 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。 RFA AG16001 规定了 3 个核心和一个总体组成部分：1) 管理（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生成的所有数据（核心 A 和 B）。来自发现阶段和复制阶段的项目 (ADSP)，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，将： 1) 创建并支持所有 CGAD 的协作网络。 、ADSP、RFA AG16002 和其他 AD 遗传学研究人员（核心 A）；协调所有遗传和表型数据并充分注释所有变异（核心 B）；所有协调和注释协议（核心 C，由核心 B 实施）；所有数据的设计分析协议（核心 C）；实施分析计划（核心 C，由核心 B 执行的计算密集型协议除外）； 5) 广泛分布的原始数据、统一的带注释的分析就绪文件和分析结果，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) 和数据库基因型和表型 (dbGaP)]（核心 B）。根据 RFA AG16001 的要求，所有协调方案和分析计划将与所有 ADSP、RFA AG16002 和其他 AD 遗传学研究人员合作进行完善。总体组件详细描述了拟议的方案。我们将使用单核苷酸变异 (SNV) 和基于基因的分析来分析复制阶段数据。我们将对复制和发现阶段的数据进行综合分析。我们还将使用非 ADSP 数据进行扩展复制阶段的数据分析，即交互分析。 ，以及多基因风险评分。这些基因发现活动将导致开发治疗方法的潜在目标。