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

项目概要/摘要 认知障碍和痴呆是普遍存在的，并导致显著的发病率和大量的经济和社会问题。 社会负担。随着美国和世界范围内痴呆症病例的增加，迫切需要 以确定预防或延迟其发作的机会。 在这个基础设施的建议中，我们建议利用遗传学的最新进展， 了解美国研究（UAS）和构建“多基因得分”（PGSs），指标，汇总 来自整个基因组的数百万遗传变异的小影响，用于社会科学研究的因素 增加或减轻阿尔茨海默病和相关痴呆症（ADRD）的风险。无人机，有可能- 在经济和社会研究中心（CESR）在大学的互联网面板 南加州，纵向跟踪美国大约10,000名成年人的样本（增长到至少10,000人）。 到2026年达到20，000人）。它结合了几个信息来源，包括调查，可穿戴设备， 行政联系，和上下文数据，并有几个独特的功能：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， 针对重大社会事件（如COVID-19）启动新数据收集的可能性 大流行），或由受访者生活中的事件引发（如当发生大流行时进行的“突发调查”）。 小组成员生活的重要变化）;它可以用来利用自然实验;它 允许频繁地收集（每月一次或两次）用户行为（来自调查的计算机用户行为，例如， 错误和处理速度），这是预测认知功能。 我们的研究不是全基因组关联研究（GWAS）。相反，我们将使用识别的遗传变异（SNP） 从现有的大型复制GWAS，创建多基因评分（PGSs），并利用独特的UAS功能， 通过其互联网操作模式提供的信息，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， 环境措施，以：（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， 通过遗传性ADRD风险推断ADRD风险/保护因素对认知的影响，以及iii）研究 遗传学在应对影响认知功能的不良生活事件中的作用。 通过公开提供大量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，等等），并通过我们自己的研究，我们寻求 鼓励在ADRD的经济和社会科学研究中使用独特的UAS能力， 以及认知能力下降。

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.