Interplay of Genetic & Socioeconomic Predictors of Memory Decline in Older Adults

遗传的相互作用

• 批准号: 8796277
• 负责人: Jessica Faul
• 金额: $ 15.55万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8796277
• 关键词: Achievement; Address; Adult; Affect; Age; Age-Years; Aging; Alzheimer' s Disease; American; Apolipoprotein E; Blood Vessels; Candidate Disease Gene; Chromosome Mapping; Chromosomes; Cognition; Cognition Disorders; Cognitive; Cohort Studies; Complex; Data; Dementia; Development; Disease; Educational Background; Elderly; Environmental Risk Factor; Episodic memory; Ethnic group; Future; Genes; Genetic; Genetic Risk; Genetic Techniques; Genomics; Genotype; Health; Heritability; Hippocampus (Brain); Human Genetics; Impaired cognition; Income; Individual; Intervention; Life Cycle Stages; Longitudinal Studies; Longitudinal Surveys; Measurable; Measures; Memory; Methodology; Methods; Modeling; Molecular; Odds Ratio; Participant; Performance; Persons; Phenotype; Prevention; Research; Respondent; Retirement; Sample Size; Sampling; Single Nucleotide Polymorphism; Socioeconomic Factors; Socioeconomic Status; Surveys; United States; Variant; Work; age related; base; cognitive function; cohort; database of Genotypes and Phenotypes; demographics; disability; gene environment interaction; genetic association; genetic variant; genome-wide; improved; innovation; interest; middle age; physical conditioning; racial and ethnic; socioeconomics; trait

DESCRIPTION (provided by applicant): Cognitive impairment and decline are prevalent among the elderly. The high estimated rate of conversion from cognitive impairment to dementia has fueled interest in the identification of genetic factors associated with cognitive impairment and its progression. Identifying predictors of which individuals will develop cognitive impairment and who will decline the fastest is necessary for better prevention and treatment of cognitive disorders. In this application, we will extend existing research by using longitudinal survey data from the Health and Retirement Study (HRS), a nationally-representative sample of adults over age 50, combined with newly- available genetic data. Specifically, this study will address four aims: Aim 1 uses a molecular-based strategy to estimate the variance in episodic memory performance and decline explained by all measured single- nucleotide polymorphisms (SNPs) and rare functional variants, both by chromosome and overall; Aim 2 investigates the gene-level and SNP-level associations of 40 genes that have significant and replicated evidence of association with episodic memory, hippocampal volume, and Alzheimer's Disease on memory performance and decline; Aim 3 develops a cumulative genetic risk score for episodic memory and compares its ability to predict memory performance and decline to demographic and socioeconomic variables; and Aim 4 examines whether socioeconomic status is a modifier of the molecular-based heritability, gene-level associations, and SNP-level associations with episodic memory and decline. This approach is innovative in its examination of both common SNPs as well as rare, potentially functional variants, its estimation of "molecular- based heritability" in cognition from unrelated individuals, and the use of state-of-the-art gene-based statistical analysis methods to examine the impact of rare functional variants in a gene region on cognitive performance and cognitive decline across racial/ethnic groups. The significance of this research lies in the improved understanding of 1) the proportion of variation in memory performance/decline that is attributable to measurable differences in genotype, 2) the impact of positional candidate genes on cognitive performance/decline in a nationally-representative sample, and 3) the degree to which genetic associations are modified by socioeconomic factors. Investigating the underlying genetic and gene-environment interactions associated with age-related memory decline may help to reveal the mechanisms of disease and provide targets for potential intervention, treatment, and prevention.

描述（由申请人提供）：认知障碍和衰退在老年人中很普遍。从认知障碍到痴呆的高估计转化率激发了人们对识别与认知障碍及其进展相关的遗传因素的兴趣。识别哪些个体将发展认知障碍以及谁将下降最快的预测因子对于更好地预防和治疗认知障碍是必要的。在本申请中，我们将通过使用来自健康与退休研究（HRS）的纵向调查数据来扩展现有研究，HRS是50岁以上成年人的全国代表性样本，结合新获得的遗传数据。具体而言，本研究将解决四个目标：目标1使用基于分子的策略来估计情景记忆表现的方差和由所有测量的单核苷酸多态性（SNP）和罕见的功能变体解释的下降，通过染色体和整体;目的2研究40个与情景记忆相关的基因的基因水平和SNP水平的关联，目标3开发了情景记忆的累积遗传风险评分，并将其预测记忆表现和衰退的能力与人口统计学和社会经济变量进行了比较;目标4检查了社会经济状况是否是基于分子的遗传力，基因水平关联和SNP水平关联与情景记忆和衰退的修饰符。该方法在以下方面具有创新性：检查常见SNP以及罕见的潜在功能性变体，估计来自无关个体的认知中的“基于分子的遗传性”，以及使用最先进的基于基因的统计分析方法来检查基因区域中的罕见功能性变体对跨种族/族裔群体的认知表现和认知下降的影响。这项研究的意义在于更好地理解1）归因于基因型可测量差异的记忆表现/下降的变化比例，2）在全国代表性样本中位置候选基因对认知表现/下降的影响，以及3）遗传关联被社会经济因素修改的程度。研究与年龄相关的记忆衰退相关的潜在遗传和基因-环境相互作用可能有助于揭示疾病的机制，并为潜在的干预，治疗和预防提供目标。