Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP)

ADSP 中阿尔茨海默病多样性遗传群体的招募和保留 (READD-ADSP)

基本信息

批准号：
10333054
负责人：
GOLDIE S. BYRD
金额：
$ 779.16万
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：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10333054
关键词：
Address Admixture Africa African African American population African Caribbean African ancestry Age Algorithms Alzheimer&apos s Disease Alzheimer&apos s disease risk Alzheimer’s disease biomarker Biocompatible Materials Biological Biological Assay Biological Markers Caribbean Hispanic Clinical Clinical Data Clinical assessments Communities DNA Data Data Collection Database Management Systems Dementia Diagnosis Disease Elderly Ethnic Origin Ethnic group European Evaluation Follow-Up Studies Future Gene Expression Genetic Genetic Diseases Genetic Predisposition to Disease Genetic Variation Genetic study Genomic approach Genomics Genotype Goals Heterogeneity Hispanic Individual Infrastructure Latinx Latinx population Neurocognitive Neurodegenerative Disorders Not Hispanic or Latino Participant Performance Pharmacological Treatment Phase Phenotype Plasma Population Population Genetics Prevention Procedures Process RNA Race Research Research Personnel Resources Risk SNP array Sampling Site Testing Underserved Population Whole Blood adjudicate adjudication base case control clinical phenotype cohort disease phenotype druggable target electronic data capture system genetic architecture genetic risk factor genome sequencing genome-wide genomic biomarker human subject protection improved new therapeutic target phenotypic data precision medicine prevent recruit risk variant transmission process whole genome

项目摘要

ABSTRACT The goal of this proposal is to create a resource for studying the genetic etiology of Alzheimer disease (AD) in understudied and underserved populations. Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. The majority of genetic studies for AD have been performed in non-Hispanic Whites (NHW) of European ancestry. While recent studies have begun expanding into other populations, these populations are still under-represented in AD genomics, particularly for cases. A major barrier to participation has been a lack of community-sensitive recruitment approaches that overcome historical mistrust of research participation. Genetic studies across populations, in particular African Americans (AA), have shown differences in both risk effect size (e.g., APOE) and risk loci (e.g., ABCA7). Further evaluation suggests that genetic ancestry (independently or interacting with environmental/cultural factors) likely underlies at least part of this heterogeneity. However, these efforts have been significantly underpowered to fully characterize genetic risk factors of AD in US individuals of African (Af) and Hispanic/Latinx (HL) Ancestry. Full characterization requires inclusion of additional populations of African genetic ancestry. To address this, we propose here the creation of a large genomics resource for the study of AD in Af and HL Ancestry. This effort will recruit, assess, sample, and genotype 13,000 individuals of diverse race/ethnicity, including 5,000 from Africa, 4,000 AA, and 4,000 HL. Clinical, phenotypic, and genetic data will be harmonized to other existing AD genomics efforts (such as the Alzheimer Disease Genetics Consortium and the Alzheimer Disease Sequencing Project; ADSP). Furthermore, we include two hypothesis-based Projects to demonstrate the utility and value of this resource and begin understanding the genetic etiology of AA and HL populations. Broadly speaking, Project 1 tests genomic and phenotypic hypotheses within cohorts, while Project 2 tests ancestry-based hypotheses across populations. These projects make extensive use of the data generated as part of this resource, as well as taking advantage of existing data from the ADSP Follow-up Study (ADSP-FUS). Through the ADSP-FUS and related studies we will access existing genomic case and control data from 13,100 African ancestry individuals, 15,900 HL individuals, and an additional 51,000 non-Hispanic whites. These studies, together with the focused resource being generated here, represent a powerful approach to understanding the totality of AD risk, with new loci and the mapping modifier loci that alter effect sizes. These studies will help illuminate the pan-population genetic architecture of AD and provide the basis for identifying druggable targets. Using ancestral populations, such those from Africa, to study risk modifiers is central to dissecting risk not only in those populations but also among AA and Caribbean Hispanics (CHI), both with significant admixture. This resource will enable improved disease prediction, prevention, diagnosis, and treatment through precision medicine, not only in in AA, Africans, and other African admixed populations, but all individuals with AD.

抽象的该提案的目标是创建研究阿尔茨海默病遗传病因学的资源（AD）在研究不足和服务不足的人群中。阿尔茨海默病（AD）是痴呆症的主要原因发生在老年人中，并发生在所有民族和种族群体中。大多数针对 AD 的遗传学研究都是在欧洲血统的非西班牙裔白人 (NHW) 中表演。虽然最近的研究已经开始扩大与其他人群相比，这些人群在 AD 基因组学中的代表性仍然不足，特别是对于病例而言。一个参与的主要障碍是缺乏对社区敏感的招聘方法来克服对研究参与的历史性不信任。跨人群的遗传研究，特别是非裔美国人 (AA)，显示出风险效应大小（例如 APOE）和风险位点（例如 ABCA7）的差异。进一步评估表明遗传祖先（独立或与环境/文化因素相互作用）可能是至少是这种异质性的一部分。然而，这些努力的力度明显不足，无法充分发挥作用。描述了美国非洲裔 (Af) 和西班牙裔/拉丁裔 (HL) 血统个体中 AD 遗传风险因素的特征。满的特征描述需要纳入具有非洲遗传血统的其他群体。为了解决这个问题，我们在此建议创建一个大型基因组学资源，用于 Af 和 HL 祖先的 AD 研究。这项努力将招募、评估、采样和基因分型 13,000 名不同种族/族裔的个体，其中 5,000 名来自非洲， 4,000 AA 和 4,000 HL。临床、表型和遗传数据将与其他现有的 AD 基因组学相协调努力（例如阿尔茨海默病遗传学联盟和阿尔茨海默病测序项目； ADSP）。此外，我们还包括两个基于假设的项目来证明该方法的实用性和价值资源并开始了解 AA 和 HL 人群的遗传病因。概括地说，项目1 测试队列内的基因组和表型假设，而项目 2 测试基于祖先的假设跨人群。这些项目广泛利用了作为该资源的一部分生成的数据，以及利用 ADSP 后续研究 (ADSP-FUS) 的现有数据。通过 ADSP-FUS 和相关研究，我们将访问来自 13,100 名非洲血统个体的现有基因组病例和对照数据， 15,900 名 HL 个人，以及另外 51,000 名非西班牙裔白人。这些研究，连同重点这里生成的资源代表了一种了解 AD 风险整体的强大方法，其中包括新的基因座和改变效应大小的映射修饰基因座。这些研究将有助于阐明泛人群 AD 的遗传结构并为识别药物靶点提供基础。利用祖先种群，对于那些来自非洲的人来说，研究风险调节因素对于剖析这些人群的风险至关重要，而且对于剖析风险也至关重要。 AA 和加勒比西班牙裔 (CHI) 之间，两者都有显着的混合。该资源将有助于改进通过精准医学进行疾病预测、预防、诊断和治疗，不仅适用于 AA、非洲人、和其他非洲混合人群，但所有个体都患有AD。