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

基本信息

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
项目类别：
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&apos s Disease Alzheimer&apos 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

项目摘要

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氏病测序项目（ADSP）是一项针对的国家测序计划确定AD的遗传风险和保护因素。项目的发现阶段包括整个外显者测序（WES）为10,061个无关的非白人西班牙裔（NHW）案例（n = 5,096）和对照（n = 4,965），以及584 NHW和西班牙家族样本的全基因组测序（WGS）。 “发现扩展” 该项目的阶段'在〜430个家族样本上增加了WGS。最初的“后续研究（FUS）” 阶段的重点是检查发现阶段的候选变体，并鉴定了新型变体通过对各种数据集的结合分析，正在进行中 “涵盖最富有的种族多样性”的无关AD案例以及高度宝贵的集合尸检确认病例和对照。总共我们已经包含在FUS中的14000多个样本中测序包括> 2800个尸检确认的病例和对照，> 6800西班牙裔（HI）案例和对照 > 5790非裔美国人（AA）案件和对照。在此FUS2应用程序中，我们正在提出测序在另外的4243个样本中，这两个样本都将增加我们找到效果的力量，但也将增强我们的能力通过包括几个丰富而独特的样品集分析。此外，这些数据集将成为广告研究社区一般的宝贵资源。总而言之 ADSP发现阶段发现的验证和概括以及新风险的发现和发现晚期发作AD（负载）的保护性变体/基因。此外，这些数据集将成为无价的广告研究社区的资源一般。具体而言，我们建议：1。增加多样性和进一步丰富了ADSP的临床表型数据，包括针对保护效果的数据集通过从实现这一目标的独特人群中的现有人群中组装样本。 2。与国家细胞存储库（NCRAD）合作，以组装DNA，血液和脑组织这些现有的队列将成为广告研究界的核心资源。 3。生成全基因组SNP阵列数据通过John P. Hussman Institute（HIHG）基因组中心技术（CGT）和整个基因组测序数据通过统一的服务大学所有收集样品4的健康科学（USUHS）。与广告数据存储的NIA遗传学合作网站（Niagads），AD基因组中心（GCAD）和宾夕法尼亚大学和HIHG 遗传流行病学和统计遗传学质量控制团队的处理，存储和传播最终数据集。我们的总体目标是增强发现广告风险和保护性的发现通过促进对种族多样化和表型丰富的数据集的AD研究的因素。