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.

项目摘要 /摘要 认知障碍和痴呆症普遍存在，引起大量发病率和大量财务， 社会伯恩。随着美国和全球痴呆症病例的增加，迫切需要 确定预防或延迟发作的机会。 在这项基础设施建议中，我们建议通过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“多基因分数”（PGSS），索引汇总 整个基因组的数百万个遗传变异的影响，用于用于因素的社会科学研究 这会增加或减轻阿尔茨海默氏病和相关痴呆症（ADRD）的风险。 UAS，概率 - 基于互联网面板位于大学经济和社会研究中心（CESR） 南加州，纵向跟踪美国约10,000名成年人的样本（至少成长为 到2026年为20,000）。它结合了几种信息来源，包括调查，可穿戴设备， 管理链接和上下文数据，并具有多个独特的功能：它为On-提供了机会 在短时间内收集数据；它允许以较高频率和 响应重大社交事件的启动新数据收集的可能性（例如COVID-19 大流行），或者是由受访者生活中的事件触发的（例如，在有一个时进行了“爆发调查” 小组成员生活的重要变化）；它可用于利用自然实验。它 允许经常收集（每月一次或两次）Paradata（来自调查的计算机用户行为，例如， 从击键中收集的错误和处理速度可以预测认知功能。 我们的不是全基因组协会研究（GWAS）。相反，我们将使用确定的遗传变体（SNP） 从现有的大型，重复的GWASS到创建多基因分数（PGS），并利用独特的UAS功能， 通过其互联网运营方式提供，以更好地了解全国代表性样本中的ADRD风险。 我们将使用PGSS以及APOE-ε4状态，以及纵向健康，认知，行为和 环境措施，至：（i）确定有认知能力下降风险的人群，（ii）收集因果关系的新数据 ADRD风险/保护因素对遗传ADRD风险认知的影响的推断，iii）研究 遗传学在影响认知功能的不良生活事件中的弹性中的作用。 通过公开提供ADRD的大量遗传措施，认知能力下降和 相关的保护/风险因素（例如体育锻炼，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），通过我们自己的研究，我们寻求 刺激在ADRD的经济和社会科学研究中使用独特的UAS功能 障碍和认知能力下降。