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

基本信息

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
项目类别：
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&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer&apos s disease related dementia Alzheimer&apos 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

项目摘要

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.

项目摘要阿尔茨海默氏病（AD）是老年痴呆症的主要原因，发生在所有种族和种族群体中。广告中的大量遗传研究已经鉴定了多个AD相关的基因和基因座，但很大一部分对AD的遗传贡献仍然未知。阿尔茨海默氏病测序项目（ADSP）正在使用大规模测序努力，以增加我们对影响AD的遗传变异的了解，特别是罕见的遗传变异，可增强AD风险或防止AD。在最近的资金浪潮中， ADSP是通过ADSP随访研究（FUS）到AG057659和AG062943的测序个体。这些努力是专门设计的，旨在改善ADSP数据集中的种族和种族多样性为NHW个体中的基因发现获得独特而强大的数据集，例如Amish保护性变体（AMISHPV）数据集，几个大型尸检确认系列和ADGC的早期发作的广告数据集。这些研究的目的是利用遗传背景的差异，可能有助于确定新的保护和风险基因座，并最终解决广告及相关的健康差异服务不足的人群中的疾病。在此应用程序中包括同伙，ADSP-FUS将执行WGS 在近30,000个人中。该应用程序的额外好处是高质量的处理和交付该应用程序中有关新队列的WGS和表型数据。具体我们建议：（1）增加多样性并通过包含约1900 AD病例和来自阿尔茨海默氏病中心（ADC）西班牙裔队列的对照，大约1500个AD病例和Faroe的控制岛屿和约3,200例AD病例和对照，来自特征良好的种族不同的A4临床试验队列；（2）与国家细胞存储库（NCRAD）紧密合作，以组装DNA和这些现有同类的血液最终将成为阿尔茨海默氏病的中心资源研究社区；（3）使用所有收集的样品生成全基因组SNP阵列数据和WGS数据已建立的资源；（4）与Niagads，GCAD和HIHG CGESG-PGNC QC团队合作将最终数据集的处理，存储和交付给Niagads以供公共数据发布；（5）和谐临床来自新获得和现有的FUS数据集的数据，以生成高质量的推断等效表型和内表型。该项目将合并几个新的同伙，以进一步增强 ADSP是阿尔茨海默氏病（AD）研究社区的宝贵资源。这些努力将加快针对所有人群的AD诊断，预防和治疗目标的发现。