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.

项目摘要/摘要 墨西哥老年人预计将面临阿尔茨海默氏病和相关痴呆症的不成比例的 （ADRD）[1]，但是考虑到这些ADRD差异的潜在环境和遗传因素是 不完全理解。这些差异的拟议机制是累积灾难理论， 其中在整个生命过程中差异暴露于不同的遗传或环境风险因素 积累以更大的ADRD患病率[2-4]积累。但是，有系统的能力 测试该理论是否因缺乏研究而阻碍了观察到的差异 墨西哥老年人的遗传和社会环境危险因素。拟议的研究将 澄清环境条件，在墨西哥老年人中，ADRD的遗传表达最大化 并最小化。首先，我将指定多种环境因素的影响（即教育，识字， 社会经济地位，乡村和移民）在ADRD风险上。其次，我将测试每个的修改作用 环境因素对载脂蛋白-E（APOE）对ADRD风险的影响。第三，我将测试修改的角色 每个环境因素对ADRD的多基因风险评分（PRS）的影响专门在人身上开发 墨西哥血统的风险。迄今为止，还没有研究研究基因的基因危险因素 墨西哥老年人的ADRD风险。拟议的研究将利用一个基于社区的大规模数据集，即 墨西哥健康与老化研究（MHA；墨西哥），墨西哥原产症的样本已成为 发达。拟议的培训和研究计划解决了以下研究问题：哪个 环境风险因素导致墨西哥老年人的ADRD风险？环境在多大程度上 墨西哥老年人普通ADRD遗传风险变异的中等影响？解决这些 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），墨西哥老年人的ADRD风险得分； 2）测试环境是否 因素中等APOEε4对墨西哥成年人LDI评分的影响； 3）测试环境因素是否 适应墨西哥原产症对墨西哥老年人LDI评分的影响。拟议的项目将是 首次阐明遗传和环境影响的研究可能是ADRD风险升高的基础 在墨西哥老年人。提高对这些因素作用的了解也将具有重要的 对公共卫生的影响，因为这项研究将提供经验证据，以告知和发展有针对性的 墨西哥老年人可能会减轻ADRD风险的干预策略。