Additional Sequencing Cohorts for the Alzheimer's Disease Sequencing Project

阿尔茨海默病测序项目的其他测序队列

• 批准号: 10241931
• 负责人: RICHARD P MAYEUX
• 金额: $ 175.85万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241931
• 关键词: African; African American; Alzheimer' s Disease; Alzheimer' s disease risk; Amish; Autopsy; Blood; Brain; Clinical Data; Cognitive; Communities; DNA; Data; Data Set; Data Storage and Retrieval; Follow-Up Studies; Genetic; Genetic Diseases; Genome; Genotype; Goals; Health Sciences; Hispanics; Indiana; Individual; Institutes; Late Onset Alzheimer Disease; National Institute on Aging; Participant; Pennsylvania; Phase; Phenotype; Population; Presenile Alzheimer Dementia; Production; Quality Control; Research; Resources; Risk Factors; SNP array; Sampling; Series; Site; Technology; Universities; University Health Services; Validation; Variant; adjudicate; arm; brain tissue; case control; cell repository; clinical phenotype; cohort; ethnic diversity; exome sequencing; genetic epidemiology; genetic risk factor; genetic variant; genome sequencing; genome-wide; human genomics; neuroimaging; novel; phenotypic data; protective allele; protective effect; protective factors; risk variant; screening; whole genome

PROJECT SUMMARY The Alzheimer's Disease Sequencing Project (ADSP) is a national sequencing initiative focused on identifying genetic risk and protective factors for AD. The projects' discovery phase includes whole exome sequencing (WES) of 10,061 unrelated non-White Hispanic (NHW) cases (N=5,096) and controls (N=4,965), and whole genome sequencing (WGS) of 584 NHW and Hispanic familial samples. The 'Discovery Extension Phase' of the project added WGS on ~430 additional familial samples. An initial 'Follow-Up Study (FUS)' Phase focused on examining candidate variants from the discovery phase, and identification of novel variants through combined analysis of diverse datasets is ongoing and focuses on additional existing cohorts with unrelated AD cases that 'encompass the richest possible ethnic diversity' as well as highly valuable set of autopsy confirmed cases and controls. In total we have already included in FUS over 14000 samples for sequencing including >2800 autopsy confirmed cases and controls, >6800 Hispanic (HI) cases and controls and > 5790 African American (AA) cases and controls. In this FUS2 application, we are proposing sequencing of an additional 4243 samples that will both increase our power to find effects but will also enhance our analysis by inclusion of several rich and unique sample sets. Additionally, these datasets will become an invaluable resource for the AD research community at-large. In summary ADSP will provide large ethnically diverse as well as unique datasets for both validation and generalization of ADSP discovery phase findings and discovery of novel risk and protective variants/genes for late onset AD (LOAD). Additionally, these datasets will become an invaluable resource for the AD research community at-large. Specifically we propose to: 1. Increase the diversity and further enrich the clinical phenotype data of the ADSP including data sets targeted to find protective effects through assembling samples from existing cohorts from unique populations that fulfill this goal. 2. Collaborate with the National Cell Repository for AD (NCRAD) in assembling DNA, blood and brain tissue on these existing cohorts, which will serve as a central resource for the AD research community. 3. Generate genome-wide SNP array data through the John P. Hussman Institute (HIHG) Center for Genome Technology (CGT) and whole genome sequencing data through the Uniformed Services University of the Health Sciences (USUHS) for all collected samples 4. Collaborate with NIA Genetics of AD Data Storage Site (NIAGADS), the Genome Center for AD (GCAD) and the University of Pennsylvania and the HIHG Center for Genetic Epidemiology and Statistical Genetics Quality Control Teams in processing, storage and dissemination of final data sets. Our overall goal is to enhance the discovery of AD risk and protective factors by facilitating research on AD in ethnically diverse and phenotypically rich datasets.

项目摘要 阿尔茨海默病测序项目（ADSP）是一项国家测序计划，重点是 确定AD的遗传风险和保护因素。该项目的发现阶段包括整个外显子组 对10，061例无关的非白人西班牙裔（NHW）病例（N= 5，096）和对照（N= 4，965）进行测序（WES）， 以及584个NHW和西班牙裔家族样本的全基因组测序（WGS）。发现扩展 该项目的“阶段”在约430个额外的家族样本上添加了WGS。初始“随访研究（FUS）” 阶段侧重于检查发现阶段的候选变体，并鉴定新变体 正在通过对不同数据集的综合分析，重点关注其他现有的队列， 不相关的AD病例“包含尽可能丰富的种族多样性”以及一组极有价值的 尸检证实的病例和对照。我们总共已经在FUS中包括了14000多个样本， 测序包括>2800例尸检确认病例和对照，>6800例西班牙裔（HI）病例和对照 和> 5790例非裔美国人（AA）病例和对照。在此FUS 2应用中，我们提出了测序 额外的4243个样本，这将增加我们发现效应的能力，但也将提高我们的 通过包含几个丰富而独特的样本集进行分析。此外，这些数据集将成为 为AD研究界提供了宝贵的资源。 总之，ADSP将为这两个方面提供大量种族多样性和独特的数据集。 ADSP发现阶段发现的验证和推广以及新风险的发现， 晚发性AD（LOAD）的保护性变体/基因。此外，这些数据集将成为 资源为AD研究社区在广大。具体而言，我们建议：1。增加多样性， 进一步丰富ADSP的临床表型数据，包括旨在发现保护作用的数据集 通过从满足这一目标的独特人群的现有队列中收集样本。2. 与国家AD细胞库（NCRAD）合作，组装DNA，血液和脑组织， 这些现有的队列，这将作为AD研究界的中心资源。3.生成 全基因组SNP阵列数据通过约翰·P·胡斯曼研究所（HIHG）基因组中心 技术（CGT）和全基因组测序数据通过统一服务大学的 健康科学（USUHS）为所有收集的样本4。与NIA Genetics合作进行AD数据存储 研究中心（NIAGADS）、AD基因组中心（GCAD）、宾夕法尼亚大学和HIHG 遗传流行病学和统计遗传学中心质量控制团队在加工，储存和 最终数据集的传播。我们的总体目标是加强AD风险的发现和保护， 通过促进在种族多样性和表型丰富的数据集中对AD的研究，