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: 9892934
• 负责人: GERARD DAVID SCHELLENBERG
• 金额: $ 215.97万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-15 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892934
• 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 Diseases; Genetic Research; Genetic study; Genomics; Genotype; Goals; Grant; Knowledge; Meta-Analysis; National Institute on Aging; Pathway Analysis; Pathway interactions; Phase; Process; Protocols documentation; Research Personnel; Risk; Single Nucleotide Polymorphism; Site; Source; Structure; Testing; Therapeutic; Time; Variant; base; case control; cost; data harmonization; data management; database of Genotypes and Phenotypes; design; exome; gene discovery; genetic variant; insertion/deletion mutation; insight; phenotypic data; polygenic risk score; prevent; protective allele; public health relevance; risk variant; therapeutic target; whole genome; 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 Diseases; Genetic Research; Genetic study; Genomics; Genotype; Goals; Grant; Knowledge; Meta-Analysis; National Institute on Aging; Pathway Analysis; Pathway interactions; Phase; Process; Protocols documentation; Research Personnel; Risk; Single Nucleotide Polymorphism; Site; Source; Structure; Testing; Therapeutic; Time; Variant; base; case control; cost; data harmonization; data management; database of Genotypes and Phenotypes; design; exome; gene discovery; genetic variant; insertion/deletion mutation; insight; phenotypic data; polygenic risk score; prevent; protective allele; public health relevance; risk variant; 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（应用程序提供）：阿尔茨海默氏病（AD）遗传学研究的目的是确定引起风险，影响风险或抵抗这种疾病的遗传变异，并确定受这些变体影响的基本基因。这些基因然后是潜在的治疗靶标。 NIA协调的阿尔茨海默氏病遗传学和基因组学中心（CGAD，本应用）是通过对所有相关数据的坐标分析来促进AD基因发现。根据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）； 3）生物统计学和数据分析核心（核心C）。根据RFA AG16001的规定，CGAD将组装由发现阶段和复制阶段的阿尔茨海默氏病序列项目（ADSP）产生的所有数据（核心A和B），以及来自非ADSP源（Core A）的所有数据，包括由RFA AG16002基于RFA AG16002所产生的。 CGAD会； 1）创建并支持所有CGAD，ADSP，RFA AG16002和其他AD遗传研究人员的协作网络（核心A）； 2）协调所有遗传和表型数据，并充分注释所有变体（核心B）； 2）设计所有协调和注释协议（核心C，由核心B实施）； 3）所有数据的设计分析协议（核心C）； 4）实施分析计划（Core C，除了将由Core B执行的计算密集型协议外）； 5）广泛分布的主要数据，协调的注释分析文件以及分析结果，包括将适当的数据存放到合格的访问数据库中[国家关于阿尔茨海默氏病遗传学的衰老遗传学研究所（NIAGADS）和基因型和表型基因型和表型（DBGAP）的数据库（CORE B）（CORE B）。按照RFA AG16001的要求，所有协调协议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核心执行的提议的活动和分析。我们将使用基于基因的分析分析复制阶段数据。将分析单个核苷酸变体（SNV）和结构变体（SV）。我们将对复制和发现阶段数据进行联合分析。我们还将使用非ADSP数据执行扩展复制阶段。我们将在途径网络分析，交互分析和多基因风险评分中分析来自所有阶段的数据。这些基因发现活动将导致发展治疗的潜在靶标。