Environmental Moderation of Genetic Influences on Dementia Risk in Mexican Older Adults

环境调节基因对墨西哥老年人痴呆风险的影响

• 批准号: 10607226
• 负责人: Kayla Tureson
• 金额: $ 4.66万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-16 至 2025-05-15
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10607226
• 关键词: Accounting; Activities of Daily Living; Address; Adult; Affect; African; Age; Aging; Alleles; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amerindian; Apolipoprotein E; Apolipoproteins; Communities; Data Set; Dementia; Development; Disadvantaged; Disparity; Economic Factors; Economics; Education; Elderly; Environmental Exposure; Environmental Risk Factor; Ethnic Population; European; European ancestry; Exclusion; Exposure to; Face; Genes; Genetic; Genetic Risk; Genetic study; Health; Healthcare; Heritability; Impaired cognition; Incidence; Individual Differences; Inequity; Intervention; Latinx; Latinx population; Life Cycle Stages; Measures; Mexican; Mexico; Minority Groups; Persons; Population; Population Heterogeneity; Prevalence; Public Health; Research; Risk; Risk Factors; Role; Sampling; Socioeconomic Status; Specific qualifier value; Subgroup; Testing; Training; Work; aging population; care burden; cognitive ability; comorbidity; dementia risk; epidemiologic data; epidemiology study; gene environment interaction; genetic risk factor; genetic variant; improved; indexing; individual variation; innovation; literacy; low socioeconomic status; migration; polygenic risk score; population based; racial population; rapid growth; risk variant; rural area; rurality; social; social factors; socioeconomic disadvantage; theories; urban area

PROJECT SUMMARY/ABSTRACT Mexican older adults are projected to face disproportionate rates of Alzheimer's disease and related dementias (ADRD) [1], but the underlying environmental and genetic factors accounting for these ADRD disparities are not fully understood. A proposed mechanism for these disparities is the cumulative disadvantage theory, wherein differential exposure to different genetic or environmental risk factors across the life course accumulate in ways that contribute to greater prevalence of ADRD [2-4]. However, the ability to systematically test whether this theory accounts for the observed disparities has been hindered by a lack of research on genetic and social environmental ADRD risk factors among Mexican older adults. The proposed study will clarify environmental conditions under which genetic expression of ADRD in Mexican older adults is maximized and minimized. First, I will specify effects of multiple environmental factors (i.e., education, literacy, socioeconomic status, rurality, and migration) on ADRD risk. Second, I will test the modifying role of each environmental factor on effects of apolipoprotein-E (APOE) on ADRD risk. Third, I will test the modifying role of each environmental factor on effects a polygenic risk score (PRS) for ADRD developed specifically in persons of Mexican ancestry on ADRD risk. No research to date has examined gene-by-environmental risk factors for ADRD risk in Mexican older adults. The proposed study will leverage a large-scale community-based dataset, the Mexican Health and Aging Study (MHAS; Mexico), the sample in which the Mexican origin PRS has been developed. The proposed training and research plan address the following research questions: Which environmental risk factors contribute to ADRD risk in Mexican older adults? To what extent do environmental risk factors moderate effects of common ADRD genetic risk variants in Mexican older adults? To address these questions, the following specific aims will be addressed: 1) Test whether the environmental factors influence ADRD risk scores in Mexican older adults via a latent dementia index (LDI); 2) Test whether environmental factors moderate APOE ε4 effects on LDI scores in Mexican adults; 3) Test whether environmental factors moderate the Mexican origin PRS effects on LDI scores in Mexican older adults. The proposed project will be the first study to elucidate the genetic and environmental influences that may underlie the elevated ADRD risk in Mexican older adults. Improved understanding of the role of these factors will also have important implications for public health, as this study will provide empirical evidence to inform and develop targeted intervention strategies that may mitigate ADRD risk among Mexican older adults.

项目概要/摘要 预计墨西哥老年人患阿尔茨海默病和相关痴呆症的比例过高 (ADRD) [1]，但造成这些 ADRD 差异的根本环境和遗传因素是 尚未完全理解这些差异的机制是累积劣势理论， 在整个生命过程中不同程度地暴露于不同的遗传或环境风险因素 累积的方式会导致 ADRD 的患病率增加 [2-4]。 检验该理论是否解释了观察到的差异是否因缺乏研究而受到阻碍 墨西哥老年人的遗传和社会环境 ADRD 危险因素。 墨西哥老年人 ADRD 基因表达最大化的环境条件 首先，我将具体说明多种环境因素的影响（即教育、识字率、 失业状况、农村和移民）对 ADRD 风险的影响 其次，我将测试每个因素的调节作用。 环境因素对载脂蛋白 E (APOE) 对 ADRD 风险影响的影响 第三，我将测试环境因素对 ADRD 风险的影响。 每个环境因素都会影响 ADRD 的多基因风险评分 (PRS)，该评分是专门针对人类开发的 墨西哥血统对 ADRD 风险的影响 迄今为止还没有研究检查基因与环境的风险因素。 墨西哥老年人的 ADRD 风险。拟议的研究将利用基于社区的大规模数据集， 墨西哥健康与老龄化研究（MHAS；墨西哥），其中墨西哥原产 PRS 已被纳入样本 拟议的培训和研究计划解决了以下研究问题： 环境风险因素对墨西哥老年人的 ADRD 风险有多大影响？ 危险因素会调节墨西哥老年人常见 ADRD 遗传风险变异的影响？ 问题，将解决以下具体目标： 1）测试环境因素是否影响 通过潜在痴呆指数 (LDI) 对墨西哥老年人进行 ADRD 风险评分 2) 测试环境是否良好 因素调节 APOE ε4 对墨西哥成年人 LDI 评分的影响 3) 测试是否有环境因素； 缓和墨西哥裔 PRS 对墨西哥老年人 LDI 分数的影响 拟议项目将是 第一项研究阐明可能导致 ADRD 风险升高的遗传和环境影响 提高对这些因素的作用的了解也将具有重要意义。 对公共卫生的影响，因为这项研究将提供经验证据来告知和制定有针对性的 可以减轻墨西哥老年人 ADRD 风险的干预策略。