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: 10371393
• 负责人: Kelly Marie Bakulski
• 金额: $ 8.37万
• 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/10371393
• 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; 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; Hispanics; Human; Individual; Inequality; Internet; Intervention; Investigation; Joints; Knowledge; Lead; Life Cycle Stages; Life Style; Measures; Mediation; Mediator of activation protein; Memory; Minority; Modeling; Modification; Molecular; Neurocognitive; Not Hispanic or Latino; Outcome; Personal Satisfaction; 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.

项目总结