GLASS-AD: Global Latinos Sequencing Study for Alzheimer's Disease

GLASS-AD：全球拉丁裔阿尔茨海默病测序研究

• 批准号: 10650278
• 负责人: Eden R. Martin
• 金额: $ 274.99万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10650278
• 关键词: Admixture; African; African American; African American population; African ancestry; Algorithms; Alzheimer' s Disease; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Americas; Amyloid beta-42; Behavior; Biological Markers; Blood; Blood specimen; Bolivia; Bolivian; Caribbean Hispanic; Clinical; Clinical Data; Cognition; Cognitive; Collaborations; Collection; Complex; DNA; Data; Data Collection; Deposition; Disease; Ensure; Environmental Risk Factor; European; Follow-Up Studies; Foundations; Frequencies; Funding; Funding Opportunities; Future; Genetic; Genetic Variation; Genetic study; Genome; Genotype; Glass; Guidelines; Health; Heterogeneity; High Prevalence; Hispanic; Hispanic Populations; Immigrant; Incidence; Indigenous; Individual; Latino Population; Maps; Methods; Mexican; Native American Ancestry; Native Americans; Not Hispanic or Latino; Peru; Peruvian; Phenotype; Plasma; Population; Population Heterogeneity; Preparation; Quechua; Research; Risk; Risk Factors; Sample Size; Sampling; Services; Site; South American; Testing; Time; Universities; Visit; adjudication; admixture mapping; biomarker panel; cell repository; cognitive testing; cohort; data sharing; data storage site; follow-up; genetic variant; genome sequencing; human genomics; innovation; mild cognitive impairment; multi-ethnic; non-genetic; polygenic risk score; rare variant; recruit; sample collection; sociodemographics; study population; tau Proteins; whole genome

ABSTRACT. Hispanics/Latinos (“HL”, genetically admixed of European [EU], African [AF] and Native American [NA] ancestry) show higher prevalence and incidence of Alzheimer's disease (AD) compared to non-Hispanic Whites. Numbers of HL and other admixed groups in the US remain insufficient to provide statistical significance in identifying risky and protective genetic variants, especially if rare. To this end, we introduce our study: Global LAtinos Sequencing Study for AD (“GLASS-AD”). We will contribute to generate necessary numbers for rare variants (RV) discovery in HL phenotyped for AD. Our proposal responds to the Alzheimer’s Disease Sequencing Project (ADSP) Follow-Up Study 2.0 (PAR 21-212) FOA, which urges to ensure appropriate representation of diverse populations in genetic studies of AD by leveraging existing cohorts and/or planning new recruitment to obtain sufficient sample sizes and power. In this study we will generate new whole genome sequencing data (WGS) in 6,000 HL: N=4,000 as part of our recently funded study “Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP” (READD-ADSP AG074865) and N=2,000 newly recruited individuals from Peru and Bolivia, leveraging the established local networks of two ongoing recruitment studies (R56AG069118; R01AG070864). GLASS-AD, together with other independent HL cohorts, will ultimately provide us with a large set of individuals with wide range of ancestry proportion, particularly for NA ancestry (8% in Caribbean Hispanics, ~50% in Mexicans, 70% in Peruvian mestizos, >90% in Peruvian and Bolivian indigenous groups). Importantly, we will increase representation of samples with substantial NA ancestry, which are needed because currently underrepresented compared to samples with predominant African ancestry (e.g., African Americans, Caribbean Hispanics). In addition to new recruitment and WGS data, we will I) generate AD-biomarkers (Aβ42, tau proteins etc.) in the 2,000 Peruvians/Bolivians and II) conduct a follow-up visit in a subset of healthy controls and mild cognitive impairment recruited by GLASS-AD in Peru/Bolivia (N=1,000) and READD-ADSP (N=1,000) at ~3 years from initial visit to assess clinical progress. We will also elucidate the association between AD and collected risk factors (cognition, health conditions and behaviors, blood biomarkers) cross-sectionally and longitudinally and perform traditional and innovative RV analyses. GLASS-AD is fully integrated with major ADSP consortia: samples will be deposited at the National Cell Repository for Alzheimer's Disease (NCRAD), genetic data will be quality controlled and harmonized following Genome Center for Alzheimer's Disease (GCAD) guidelines, deposited and shared by NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS). GLASS data will be shared with the ADSP Follow-Up Study (“FUS” AG057659, AG062943 and AG076482), which is sequencing several independent HL cohorts and will ensure the largest collection of HL with WGS data. Importantly, our analyses methods will be harmonized with ongoing ADSP analyses consortia (e.g. Collaborative for Alzheimer’s Disease Research [CADRE]).

摘要。西班牙裔/拉丁裔（“HL”，在基因上混合了欧洲人 [EU]、非洲人 [AF] 和美洲原住民 与非西班牙裔人相比，[NA] 血统）显示阿尔茨海默病 (AD) 的患病率和发病率更高 美国 HL 和其他混合群体的数量仍然不足以提供统计数据。 在识别风险性和保护性遗传变异方面具有重要意义，特别是在罕见的情况下。 研究：全球 LAtinos AD 测序研究（“GLASS-AD”） 我们将致力于产生必要的信息。 AD 表型 HL 中罕见变异 (RV) 发现的数量。 阿尔茨海默病测序项目 (ADSP) 后续研究 2.0 (PAR 21-212) FOA，敦促确保 通过利用现有队列和/或在 AD 遗传研究中适当代表不同人群 规划新的招募以获得足够的样本量和功效在本研究中我们将产生新的整体。 6,000 HL 的基因组测序数据 (WGS)：N=4,000，作为我们最近资助的研究“招募和招募”的一部分 “ADSP 中阿尔茨海默病多样性遗传群体的保留”(READD-ADSP AG074865) 和 N=2,000 名来自秘鲁和玻利维亚的新招募人员，利用两个国家已建立的本地网络 与其他独立 HL 一起正在进行的招募研究（R56AG069118；R01AG070864）。 群体，最终将为我们提供一大群具有广泛血统比例的个体，特别是 北美血统（加勒比西班牙裔为 8%，墨西哥人为 50%，秘鲁混血人为 70%，秘鲁人为 >90%） 重要的是，我们将增加大量样本的代表性。 NA 血统，这是必需的，因为与占主导地位的样本相比，目前代表性不足 非洲血统（例如非裔美国人、加勒比西班牙裔）除了新招募和 WGS 数据外， 我们将 I) 在 2,000 名秘鲁人/玻利维亚人中生成 AD 生物标志物（Aβ42、tau 蛋白等），并且 II) 进行 对 GLASS-AD 招募的健康对照和轻度认知障碍子集进行随访 秘鲁/玻利维亚 (N=1,000) 和 READD-ADSP (N=1,000) 在初次就诊后约 3 年评估临床进展。 我们还将阐明 AD 与收集到的风险因素（认知、健康状况和 行为、血液生物标志物）横向和纵向，并执行传统和创新的 RV GLASS-AD 与主要的 ADSP 联盟完全集成：样本将存放在国家实验室。 阿尔茨海默病细胞存储库 (NCRAD)，遗传数据将受到质量控制和协调 遵循阿尔茨海默病基因组中心 (GCAD) 指南，由 NIA Genetics 保存和共享 阿尔茨海默病数据存储站点 (NIAGADS) 数据将与 ADSP 后续研究共享。 （“FUS”AG057659、AG062943 和 AG076482），正在对几个独立的 HL 队列进行测序，并将 确保最大程度地收集 HL 和 WGS 数据。重要的是，我们的分析方法将与 WGS 数据保持一致。 正在进行的 ADSP 分析联盟（例如阿尔茨海默病研究协作组织 [CADRE]）。