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; 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）：老年人中普遍存在认知障碍和下降。从认知障碍到痴呆症的高估计率转化率高于鉴定与认知障碍及其进展相关的遗传因素的兴趣。确定个人将发展认知障碍的预测因素，以及谁将拒绝最快的人是更好地预防和治疗认知障碍所必需的。在此应用程序中，我们将通过使用健康和退休研究（HRS）的纵向调查数据（HRS）扩展现有研究，这是50岁以上的全国代表性样本，再加上新近可用的遗传数据。具体而言，这项研究将解决四个目标：AIM 1使用基于分子的策略来估算所有测得的单核苷酸多态性（SNP）和稀有功能变体的差异，并通过染色体和整体来解释。 AIM 2研究了40个基因的基因级和SNP级关联，这些基因与情节记忆，海马体积和阿尔茨海默氏病有关的大量且复制的证据就记忆力表现和下降； AIM 3为情节记忆发展了累积的遗传风险评分，并将其预测记忆力和衰落的能力与人口统计和社会经济变量进行了比较； AIM 4研究了社会经济地位是否是基于分子的遗传力，基因级关联以及SNP级关联与情节记忆和下降的联系。这种方法在检查普通SNP以及罕见的，潜在的功能性变异的研究中具有创新性，其在无关个体的认知中对“基于分子的遗传力”的估计以及基于最先进的基因基因统计分析方法的使用，用于检查稀有功能变体对跨认知性能和跨种族差异的稀有功能变异的影响。这项研究的意义在于对1）记忆性能/下降的变化比例的改善，这归因于基因型的可测量差异，2）位置候选基因对全国证实样本中认知性能/下降的影响，以及3）社会经济学因素对哪种遗传关联进行了修改的程度。研究与年龄相关记忆下降相关的基本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。