Genotyping the Understanding America Study to generate novel opportunities for research on cognitive functioning and dementia

对“理解美国研究”进行基因分型，为认知功能和痴呆症研究创造新机会

• 批准号: 10663049
• 负责人: Jessica Faul
• 金额: $ 276.32万
• 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: 2023-09-15 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10663049
• 关键词: Address; Adult; Affect; Alzheimer' s Disease; Alzheimer' s disease related dementia; Area; Behavior; Behavioral; COVID-19 pandemic; California; Caregivers; Cessation of life; Cognition; Cognitive; Collection; Communities; Complex; Computers; Creativeness; DNA; Data; Data Collection; Dementia; Diabetes Mellitus; Diet; Economics; Education; Educational workshop; Employment; Environment; Event; Family; Frequencies; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genetic study; Genome; Genotype; Glean; Health; Hypertension; Impaired cognition; Individual; Infrastructure; Internet; Life; Measures; Monitor; Morbidity - disease rate; National Institute on Aging; Natural experiment; Neurobehavioral Manifestations; Obesity; Occupations; Outcome; Participant; Phenotype; Physical activity; Physical environment; Policies; Policy Maker; Pollution; Populations at Risk; Probability; Publishing; Quasi-experiment; Recording of previous events; Research; Research Personnel; Respondent; Risk; Risk Factors; Role; Salivary; Sampling; Sleep; Smoking; Social Environment; Social Sciences; Societies; Source; Standardization; Surveys; Tablets; Unemployment; Universities; Variant; Weight; apolipoprotein E-4; behavioral response; cardiovascular risk factor; cognitive function; data storage site; dementia risk; field survey; genetic variant; genome wide association study; indexing; innovation; member; novel; operation; phenotypic data; prevent; processing speed; protective factors; recruit; resilience; response; risk mitigation; social; social science research; trait; wearable device

Project summary / abstract Cognitive impairment and dementia are prevalent and cause significant morbidity and substantial financial and social burden. With the rising number of cases of dementia in the U.S. and worldwide, there is an urgent need to identify opportunities for preventing or delaying its onset. In this infrastructure proposal, we propose to make use of recent advances in genetics by genotyping the Understanding America Study (UAS) and constructing “polygenic scores” (PGSs), indexes that aggregate the small effects of millions of genetic variants from across the genome, for use in social-science studies of factors that increase or mitigate the risk of Alzheimer’s Disease and Related Dementias (ADRD). The UAS, a probability- based Internet panel housed at the Center for Economic and Social Research (CESR) at the University of Southern California, longitudinally tracks a sample of approximately 10,000 adults in the U.S. (growing to at least 20,000 by 2026). It combines several sources of information, including from surveys, wearable devices, administrative linkages, and contextual data, and has several unique features: it provides the opportunity for on- demand data collection on short notice; it allows for the collection of data at higher frequencies and for the possibility of initiating new data collection in response to major societal events (such as the COVID-19 pandemic), or triggered by events in the lives of respondents (such as “burst surveys” fielded when there is an important change in the life of a panel member); it can be used to take advantage of natural experiments; it allows for frequent collection (once or twice a month) of paradata (computer user-behavior from surveys, e.g., errors and processing speed gleaned from keystrokes) which is predictive of cognitive functioning. Ours is not a genome-wide association study (GWAS). Instead, we will use genetic variants (SNPs) identified from existing large, replicated GWASs, to create polygenic scores (PGSs), and exploit unique UAS capabilities, afforded by its Internet mode of operation, to better understand ADRD risk in a nationally representative sample. We will use PGSs, as well as APOE-ε4 status, together with longitudinal health, cognitive, behavioral, and environmental measures, to: (i) identify populations at risk of cognitive decline, (ii) collect new data for causal inferences of the effects of ADRD risk/protective factors on cognition by genetic ADRD risk, and iii) study the role of genetics in the resilience to adverse life events affecting cognitive functioning. By making publicly available a large number of genetic measures for ADRD, cognitive decline, and associated protective/risk factors (e.g., physical activity, cardiovascular risk [diabetes, obesity, smoking and hypertension], diet, sleep, pollution, and education, among others), and through our own research, we seek to stimulate the use of unique UAS capabilities in economic and social-science research of ADRD, cognitive impairment, and cognitive decline.

项目概要/摘要 认知障碍和痴呆症很普遍，导致严重的发病率和巨大的财务和损失 社会负担。随着美国和世界范围内痴呆症病例数量的不断增加，迫切需要 以确定预防或延迟其发生的机会。 在这个基础设施提案中，我们建议通过对基因进行基因分型来利用遗传学的最新进展 了解美国研究 (UAS) 并构建“多基因评分”(PGS)，即汇总 来自整个基因组的数百万个遗传变异的微小影响，用于因素的社会科学研究 增加或减轻阿尔茨海默病和相关痴呆症 (ADRD) 的风险。 UAS，概率- 位于大学经济和社会研究中心 (CESR) 的互联网小组 南加州纵向追踪了美国大约 10,000 名成年人的样本（增长到至少 到 2026 年将达到 20,000）。它结合了多种信息来源，包括调查、可穿戴设备、 管理联系和上下文数据，并具有几个独特的功能：它提供了机会 要求在短时间内收集数据；它允许以更高的频率收集数据，并且 启动新数据收集以应对重大社会事件（例如 COVID-19）的可能性 流行病），或由受访者生活中的事件触发（例如在出现疫情时进行的“突发调查”） 小组成员生活中的重大变化）；它可以用来利用自然实验；它 允许频繁收集（每月一次或两次）参数数据（调查中的计算机用户行为，例如， 从击键中收集的错误和处理速度）可以预测认知功能。 我们的研究不是全基因组关联研究（GWAS）。相反，我们将使用已识别的遗传变异 (SNP) 从现有的大型、复制的 GWAS 中，创建多基因评分 (PGS)，并利用独特的 UAS 功能， 通过其互联网运营模式，更好地了解全国代表性样本中的 ADRD 风险。 我们将使用 PGS 以及 APOE-ε4 状态，以及纵向健康、认知、行为和 环境措施，以：(i) 识别有认知能力下降风险的人群，(ii) 收集新的因果数据 通过遗传 ADRD 风险推断 ADRD 风险/保护因素对认知的影响，以及 iii) 研究 遗传学在对影响认知功能的不良生活事件的恢复力中的作用。 通过公开大量针对 ADRD、认知能力下降和 相关的保护/风险因素（例如体力活动、心血管风险[糖尿病、肥胖、吸烟和 高血压]、饮食、睡眠、污染和教育等），并且通过我们自己的研究，我们力求 刺激在ADRD、认知等经济和社会科学研究中使用独特的无人机系统能力 障碍和认知能力下降。