DNA Methylation,Genetics, and Modifiable Risk Factors of Dementia in a Nationally Representative, Multi-Ethnic Cohort

具有全国代表性的多种族队列中痴呆症的 DNA 甲基化、遗传学和可改变的危险因素

• 批准号: 10374124
• 负责人: Kelly Marie Bakulski
• 金额: $ 75.15万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10374124
• 关键词: Adult; Affect; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Base Sequence; Behavioral; Biological; Biological Markers; Biology; Black race; Blood Pressure; Body mass index; Characteristics; Clinical assessments; Cognition; Collaborations; Complex; DNA Methylation; Data; Databases; Dementia; Development; Diabetes Mellitus; Disease; Education; Ensure; Environment; Environmental Risk Factor; Epidemiology; Epigenetic Process; Ethnic Origin; Ethnic group; Etiology; Evaluation; Genetic; Genetic Polymorphism; Genetic Risk; Genome; Geography; Goals; Health; Health and Retirement Study; Hispanic; Human; Individual; Inequality; Internet; Intervention; Investigation; Joints; Knowledge; Lead; Life Cycle Stages; Life Style; Measures; Mediation; Mediator of activation protein; Memory; Minority; Minority Women; Modeling; Modification; Molecular; Neurocognitive; Not Hispanic or Latino; Outcome; Personal Satisfaction; Persons; Phenotype; Physical activity; Physiological; Population; Positioning Attribute; Prevalence; Protocols documentation; Public Health; Race; Recording of previous events; Research; Risk; Risk Factors; Role; Rural; Sample Size; Sampling; Site; Smoking; Source; Testing; United States; Woman; Work; age group; aging demographic; cognitive testing; cohort; dementia risk; depressive symptoms; epigenetic marker; health disparity; improved; methylation testing; modifiable risk; multi-ethnic; novel strategies; peripheral blood; potential biomarker; pre-clinical; prediction algorithm; psychosocial; racial and ethnic; sex; social; social factors; symposium; tool

PROJECT SUMMARY Alzheimer’s disease and its related dementias (ADRD) represent the leading terminal forms of dementia affecting a growing number of aging adults in the United States. Biomarkers of ADRD risk, particularly among susceptible populations (ADRD risk is disproportionately high among minorities, women, rural inhabitants, and people with lower education), represent a critical knowledge gap. Thus, studies with sufficient sample sizes, concurrently assessing multiple characteristics, such as educational attainment, environment, social, behavioral, lifestyle, geographic, biology, and epigenetics, will be uniquely positioned to effectively test factors or combinations of factors that create and sustain ADRD disparities. Our goal is to determine the joint epigenetic and environmental contributions to ADRD risk that underlie these health disparities. Using existing epigenetic and genetic data, well-characterized dementia phenotypes, and diverse risk factor data, we will analyze a population representative, multi-ethnic aging sample from the Health and Retirement Study (HRS). We aim to (1) test the associations between DNA methylation and dementia phenotypes (prevalent, 8-year incident), stratified by race/ethnicity and test for effect modification by ADRD disparity-related factors (educational attainment, sex, urban/rural); (2) identify associations between longitudinal measures of modifiable risk factors for ADRD and DNA methylation, stratified by race/ethnicity and test for effect modification or mediation by ADRD disparity-related factors; and finally, (3) identify genetic polymorphisms controlling DNA methylation and whether these are enriched in dementia outcomes to evaluate the role of DNA methylation in disease development. This study will likely impact the field of Alzheimer’s research and contribute to public health because it will a) establish the relevance of DNA methylation on ADRD in multiple race/ethnicities; b) elucidate important biological epigenetic mechanisms; c) determine the combined and individual epigenetic-environment interplay contributions to ADRD; and d) consider the effects of sex, educational attainment, race/ethnicity, younger age groups, and urban/rural status in the same study where comparisons of relative contribution to risk can be made. Here, we have the opportunity to simultaneously and substantially improve our understanding of the genetic and environmental etiologic contributions to health disparities in ADRD.

项目摘要 阿尔茨海默氏病及其相关痴呆症（ADRD）代表了领先的终末形式 痴呆会影响美国越来越多的衰老成年人。 Adrd的生物标志物 风险，尤其是在易感人群中（ADRD风险在 少数民族，妇女，农村居民和受教育程度较低的人）是关键的 知识差距。这是具有足够样本量的研究，同时评估了多个 特征，例如教育，环境，社会，行为，生活方式， 地理，生物学和表观遗传学将是有效测试因素或 造成和维持ADRD差异的因素的组合。我们的目标是确定 对这些健康的基础的联合表观遗传和环境贡献 差异。使用现有的表观遗传学和遗传数据，特征良好的痴呆表型， 和潜水的风险因素数据，我们将分析人群代表多种族老龄化的人群 来自健康和退休研究（HRS）的样本。我们的目标是（1）测试关联 DNA甲基化和痴呆表型（流行，8年入射）之间，分层 种族/民族和通过ADRD差异相关的因素（教育）进行效果修改测试 成就，性别，城市/农村）； （2）确定纵向测量之间的关联 ADRD和DNA甲基化的可修改风险因素，通过种族/种族进行分层和测试 通过与ADRD差异相关的因素进行修改或调解；最后，（3）确定 控制DNA甲基化的遗传多态性以及它们是否富含 痴呆症结果评估DNA甲基化在疾病发育中的作用。这项研究 可能会影响阿尔茨海默氏症研究领域并为公共卫生做出贡献，因为它将 a）在多种种族/种族中确定DNA甲基化对ADRD的相关性； b）阐明 重要的生物学表观遗传机制； c）确定合并和个人 对ADRD的表观遗传环境相互作用贡献； d）考虑性的影响， 同样 研究可以比较对风险的相对贡献。在这里，我们有 有机会简单地增强我们对遗传和遗传的理解 环境病因对ADRD的健康分配贡献。