Additional Sequencing for the Alzheimer's Disease Sequencing Project (ADSP)

阿尔茨海默病测序项目 (ADSP) 的附加测序

• 批准号: 10473656
• 负责人: MICHAEL L CUCCARO
• 金额: $ 520.29万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10473656
• 关键词: Address; African American; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amish; Autopsy; Blood; Classification; Clinical Data; Clinical Trials; Cognitive; Communities; County; DNA; Data; Data Element; Data Set; Dementia; Diagnostic; Disease; Early Onset Alzheimer Disease; Elderly; Ethnic group; Faeroe Islands; Follow-Up Studies; Funding; Genetic; Genetic Variation; Genetic study; Genome; Genotype; Hispanic; Hispanic Populations; Individual; Institutes; Knowledge; Large-Scale Sequencing; Methods; Participant; Phase; Phenotype; Population; Prevention; Process; Production; Quality Control; Race; Research; Resources; SNP array; Sampling; Series; Special Population; Speed; Technology; Underserved Population; Variant; Work; adjudicate; case control; cell repository; clinical phenotype; clinically relevant; cohort; design; endophenotype; ethnic diversity; exome sequencing; gene discovery; genetic risk factor; genetic variant; genome sequencing; genome-wide; genomic locus; health disparity; human genomics; improved; novel; phenotypic data; protective allele; racial diversity; risk variant; screening; whole genome

PROJECT SUMMARY Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. A multitude of genetic studies in AD have identified multiple AD associated genes and loci, but a large portion of the genetic contribution to AD remains 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. In the most recent wave of funding, the ADSP is sequencing individuals from the ADSP Follow-up Study (FUS) through AG057659 and AG062943. These efforts were specifically designed to improve racial and ethnic diversity in the ADSP datasets as well as to acquire unique and powerful data sets for gene discovery in NHW individuals, such as the Amish protective variant (AMISHPV) dataset, several large autopsy-confirmed series and the ADGC's early-onset AD dataset. The purpose of these studies has been to capitalize on differences in genetic backgrounds that may facilitate the identification of new protective and risk loci and ultimately address health disparities for AD and related disorders in underserved populations. Including the cohorts in this application, the ADSP-FUS will perform WGS on nearly 30,000 individuals. An added benefit of this application is the processing and delivery of high quality WGS and phenotype data on the new cohorts in this application. Specifically we propose to: (1) Increase the diversity and further enrich the clinical phenotype data of the ADSP through inclusion of ~1900 AD cases and controls from the Alzheimer Disease Center (ADC) Hispanic cohort, ~1500 AD cases and controls from the Faroe Islands, and ~3,200 AD cases and controls from the well characterized ethnically diverse A4 Clinical Trial Cohort; (2) work closely with the National Cell Repository for Alzheimer's Disease (NCRAD) in assembling DNA and blood on these existing cohorts which will ultimately serve as a central resource for the Alzheimer's disease research community; (3) generate genome-wide SNP array data and WGS data for all collected samples using established resources; (4) collaborate with NIAGADS, GCAD and the HIHG CGESG-PGNC QC Teams in processing, storage, and delivery of final datasets to NIAGADS for public data release; and (5) harmonize clinical data from newly acquired and existing FUS datasets to generate high quality inferentially equivalent phenotypes and endophenotypes. This project will merge several new cohorts into the ADSP-FUS to further enhance the ADSP as an invaluable resource for the Alzheimer's disease (AD) research community. These efforts will speed discoveries of targets for AD diagnosis, prevention, and treatment for all populations.

项目概要 阿尔茨海默病（AD）是老年人痴呆的主要原因，发生在所有民族和种族群体中。 大量 AD 遗传学研究已经确定了多个 AD 相关基因和基因座，但其中很大一部分 AD 的遗传因素仍然未知。阿尔茨海默病测序项目 (ADSP) 正在使用 大规模测序工作以增加我们对影响 AD 的遗传变异的了解， 特别罕见的基因变异会增加 AD 风险或预防 AD。在最近一波融资中， ADSP 正在对 ADSP 后续研究 (FUS) 至 AG057659 和 AG062943 中的个体进行测序。 这些努力是专门为了改善 ADSP 数据集中的种族和民族多样性以及 获取独特而强大的数据集，用于 NHW 个体的基因发现，例如阿米什人的保护性 变体（AMISHPV）数据集、几个大型尸检证实的系列和 ADGC 的早发 AD 数据集。 这些研究的目的是利用遗传背景的差异，这可能有助于 识别新的保护性和风险位点，并最终解决 AD 和相关疾病的健康差异 服务不足的人群中的疾病。包括本申请中的队列，ADSP-FUS 将执行 WGS 涉及近 30,000 人。该应用程序的另一个好处是高质量的处理和交付 本申请中新群体的全基因组测序和表型数据。具体来说，我们建议：（1）增加 通过纳入约 1900 个 AD 病例和进一步丰富 ADSP 的临床表型数据 来自阿尔茨海默病中心 (ADC) 西班牙裔队列的对照，约 1500 例 AD 病例和来自法罗群岛的对照 岛屿，以及约 3,200 例 AD 病例和对照，这些病例来自特征明确的种族多样化 A4 临床试验队列； (2) 与阿尔茨海默病国家细胞存储库（NCRAD）密切合作，组装 DNA 并 这些现有人群的血液最终将成为阿尔茨海默病的核心资源 研究团体； (3) 使用以下方法为所有收集的样本生成全基因组 SNP 阵列数据和 WGS 数据 已建立的资源； (4) 与 NIAGADS、GCAD 和 HIHG CGESG-PGNC QC 团队合作 处理、存储最终数据集并将其交付给 NIAGADS 以供公共数据发布； (5) 协调临床 来自新获取和现有 FUS 数据集的数据，以生成高质量的推断等效表型 和内表型。该项目将把几个新群体合并到 ADSP-FUS 中，以进一步增强 ADSP 是阿尔茨海默病 (AD) 研究界的宝贵资源。这些努力将加速 发现针对所有人群的 AD 诊断、预防和治疗目标。