Genes, environments, interactions, and cognitive decline in the HRS

HRS 中的基因、环境、相互作用和认知能力下降

基本信息

批准号：
8928537
负责人：
Kathleen M Hayden
金额：
$ 29.3万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-30 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8928537
关键词：
Age Alzheimer&apos s Disease Alzheimer&apos s disease risk Apolipoprotein E Brain-Derived Neurotrophic Factor CASP1 gene Cognition Cognitive Complex Coupled Data Development Disease Education Environment Environmental Exposure Environmental Risk Factor Epidemiology Functional disorder Gene Combinations Genes Genetic Genetic Epistasis Genotype Health Homeostasis Impaired cognition Impairment Income Individual Inflammation Inflammatory Inherited Interferons Interleukin-10 Interleukin-6 Intervention Late Onset Alzheimer Disease Longitudinal Studies MTHFR gene Measures Mental Depression Methods Modeling Modification Neighborhoods Outcome Participant Pathway interactions Pattern Performance Peroxisome Proliferator-Activated Receptors Phase Phenotype Poverty Prevalence Prevention strategy Public Assistance Retirement Risk Role Sampling Socioeconomic Status Stress TNF gene Telephone Interviews Testing Time Unemployment base cardiovascular disorder risk cardiovascular risk factor cognitive function cognitive testing disorder prevention effective therapy environmental stressor follow-up forest gene environment interaction gene interaction genetic epidemiology genetic risk factor genome wide association study health data interest low socioeconomic status neuropathology pre-clinical risk variant targeted treatment time use trait

项目摘要

DESCRIPTION (provided by applicant): Genes, environments, interactions, and cognitive decline in the HRS Project Summary: Alzheimer's disease (AD) is a heterogeneous disease with a potentially wide range of contributing environmental and genetic risk factors. A long pre-clinical period of cognitive decline accompanies the accumulation of neuropathology and precedes the onset of AD. Navigating the many pathways to cognitive decline and dysfunction requires a multifaceted approach that incorporates both epidemiology and genetics. The role of epidemiology is crucial for identifying modifiable factors that may reduce AD risk; the role of genetics in AD has proven to be very complex. Early studies identified genes in the inflammatory pathways and genes associated with stress. Although some of these genes have shown evidence of environmental interactions, few have been investigated for interactions in AD and few have been replicated in genome wide association studies (GWAS). Instead, GWAS have yielded risk genes with relatively small effects, many of which have been tied to cognitive decline as well as AD. We propose to study interactions between AD risk genes, genes from the inflammatory pathway, environmental risk factors, and their combined influence on cognitive decline. Such interactions could explain a portion of AD prevalence that is currently unexplained. The Health and Retirement Study (HRS) longitudinal data coupled with newly released GWA data from over 11,000 participants age 65 and older provides an ideal opportunity to study these associations in a powerful way. Using latent trajectory models, we will define groups of individuals based on cognitive test performance over time. Using random forests, we will study the associations between cognitive trajectories and AD risk genes, inflammation genes, environmental factors, and their interactions. This approach, combining complex methods, will allow us to study in greater detail the interrelationships between genes, environments, and their interactions as they influence the rate of cognitive decline.

描述（由申请人提供）：HRS项目摘要中的基因，环境，相互作用和认知下降：阿尔茨海默氏病（AD）是一种异质性疾病，具有广泛的环境和遗传危险因素。长期的临床前认知下降时期伴随着神经病理学的积累，并在AD的发作之前。导航许多认知能力下降和功能障碍的途径需要一种多方面的方法，该方法同时结合了流行病学和遗传学。流行病学的作用对于确定可能降低AD风险的可修改因素至关重要；事实证明，遗传学在AD中的作用非常复杂。早期研究确定了与压力相关的炎症途径和基因中的基因。尽管其中一些基因显示了环境相互作用的证据，但在基因组广泛的关联研究（GWAS）中，很少有人研究过AD的相互作用，很少有人复制。取而代之的是，GWAS产生的风险基因具有相对较小的影响，其中许多与认知能力下降和AD相关。我们建议研究AD风险基因，炎症途径，环境风险因素的基因及其对认知能力下降的综合影响之间的相互作用。这种相互作用可以解释当前无法解释的AD流行率的一部分。健康与退休研究（HRS）纵向数据以及来自65岁及以上年龄较大的11,000多名参与者的新发布的GWA数据为以强大的方式研究这些关联提供了理想的机会。使用潜在轨迹模型，我们将根据认知测试的表现定义个体组。使用随机森林，我们将研究认知轨迹与AD风险基因，炎症基因，环境因素及其相互作用之间的关联。这种方法结合了复杂的方法，将使我们能够更详细地研究基因，环境及其相互作用之间的相互关系，因为它们会影响认知能力下降的速度。