Genetic Differences in the Causal Effect of Education Quantity and Quality on Cognitive Functioning and Dementia Diagnosis Later in Life

教育数量和质量对晚年认知功能和痴呆症诊断的因果影响的遗传差异

• 批准号: 10707517
• 负责人: Silvia Helena Barcellos
• 金额: $ 78.89万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10707517
• 关键词: Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Automobile Driving; Behavioral; Body mass index; Cessation of life; Characteristics; Childhood; Clinical; Cognition; Cognitive; Conceptions; Data; Data Set; Dementia; Diagnosis; Education; Educational Curriculum; Elderly; Family; Finland; Genes; Genetic; Genetic Databases; Genetic Risk; Genotype; Geography; Health; Hospitalization; Impaired cognition; Individual; Intelligence; International; Intervention; Knowledge; Life; Life Expectancy; Link; Liquid substance; Measures; Natural experiment; Netherlands; Outcome; Parents; Participant; Persons; Policies; Policy Maker; Prevalence; Process; Pupil; Registries; Research; Respondent; Risk Factors; Role; Running; Sampling; Schools; Smoking; Source; Student Selections; Students; Surveys; Variant; Vocation; aging population; biobank; cognitive function; cognitive testing; cohort; conditioning; dementia risk; design; disparity reduction; family genetics; genetic analysis; health disparity; health record; higher education; human old age (65+); improved; indexing; primary care visit; processing speed; prospective memory; residence; teacher; visual memory

Project Summary/Abstract Gains in life expectancy and population aging are driving a sharp rise in Alzheimer's Disease and Related Dementias (ADRD). In this context, it is crucial to understand what factors can modify ADRD risk and cognitive decline in older ages. Education has been identified as one potential modifier, as higher education is robustly associated with lower ADRD risk. However, little is known about how much of this association reflects a causal effect from education to ADRD risk and how much is driven by common third factors, such as genetics, that may confound and moderate this relationship. In addition, the relevance of factors beyond the quantity of education – in particular the importance of education quality as a driver of ADRD risk, as well as a moderator in the relationship between education and ADRD – are not well understood. Filling these knowledge gaps is essential to the design of effective policies aimed at improving cognitive health and reducing disparities in ADRD risk. In this project, we propose to study how much of the association between education, cognition and ADRD risk in late-life is due to a causal effect running from education quantity and quality to cognition/ADRD risk. To deal with the fact that different people self-select into different types and quantities of schooling, we will use two natural experiments: one school reform that affected education quantity (years of compulsory schooling) and another that affected quality (academic curriculum). We will supplement existing datasets with the construction of polygenic indexes (PGIs) for educational attainment (EA) and for Alzheimer's Disease (AD), and by linking participants to local historic school quality measures such as pupil/teacher ratios and teacher pay. This will allow us to study the role of genetics and school quality in moderating the effects of both school reforms on ADRD. We will use data from three large international aging cohorts: the UK Biobank (UK), FinnGen (Finland) and Lifelines (the Netherlands). These cohorts allow us to study administrative-based measures of ADRD diagnosis, ADRD risk factors and survey-based measures of cognition. Moreover, the three cohorts were genotyped, allowing us to explore the role of genetics in driving ADRD risk as well as in moderating the relationship between education and ADRD risk. Establishing whether education has a causal effect on late-life cognition and ADRD risk is challenging but essential for identifying clinical and policy interventions. Without causal evidence, policy makers do not know whether education improves individuals' later-life cognitive health or whether the education-ADRD association reflects differences in the characteristics of individuals who self-select into education. Moreover, it is equally important to know what aspects of education causally affect ADRD risk. What is the relative benefit of increasing the quantity of education versus improving its quality? Are individuals who are predicted to get more education based on their genes protected against genetic risk of AD? The lack of such knowledge limits the design of policies aimed at reducing disparities in ADRD risk. Our project aims to start filling these knowledge gaps.

项目总结/摘要 预期寿命的增加和人口老龄化正在推动阿尔茨海默病和相关疾病的急剧上升。 痴呆症（ADRD）。在这种情况下，了解哪些因素可以改变ADRD风险和认知功能是至关重要的。 老年人减少。教育被认为是一个潜在的调整因素，因为高等教育是一个强有力的因素。 与较低的ADRD风险相关。然而，很少有人知道这种联系在多大程度上反映了一种因果关系。 教育对ADRD风险的影响，以及有多少是由常见的第三因素（如遗传学）驱动的，这可能 破坏和缓和这种关系。此外，教育量以外的相关因素 - 特别是教育质量作为ADRD风险的驱动因素以及ADRD风险的调节因素的重要性， 教育和ADRD之间的关系-没有得到很好的理解。填补这些知识空白至关重要 设计有效的政策，旨在改善认知健康和减少ADRD风险的差异。 在这个项目中，我们建议研究教育，认知和ADRD风险之间的关联程度 是由于从教育数量和质量到认知/ADRD风险的因果关系。处理 由于不同的人自我选择不同类型和数量的学校教育，我们将使用两个 自然实验：一所学校的改革影响了教育质量（义务教育年限）， 另一个影响质量（学术课程）。我们将通过构建 多基因指数（PGIs）的教育程度（EA）和阿尔茨海默病（AD），并通过连接 参与者可以根据当地历史悠久的学校质量标准，如学生/教师比例和教师工资。这将允许 我们研究遗传学和学校质量在调节学校改革对ADRD的影响中的作用。 我们将使用来自三个大型国际老龄化队列的数据：英国生物银行（英国），FinnGen（芬兰）和 生命线（荷兰）。这些队列使我们能够研究ADRD诊断的基于管理的措施， ADRD风险因素和基于调查的认知测量。此外，对这三个队列进行了基因分型， 这使我们能够探索遗传学在驱动ADRD风险以及调节ADRD与ADRD之间关系中的作用。 教育和ADRD风险。 确定教育是否对晚年认知和ADRD风险有因果关系是具有挑战性的， 对于确定临床和政策干预至关重要。没有因果关系的证据，决策者不知道 教育是否改善了个体的晚年认知健康，或者教育与ADRD的关系是否 反映了自我选择接受教育的个体的特征差异。此外，它同样 重要的是要知道教育的哪些方面会影响ADRD风险。增加的相对效益是什么 教育的数量与提高教育质量之间的关系？是那些被预测接受更多教育的人 是基于他们的基因可以保护他们不受AD遗传风险的影响吗？这种知识的缺乏限制了 旨在减少ADRD风险差异的政策。我们的项目旨在填补这些知识空白。

项目成果

Overcoming attenuation bias in regressions using polygenic indices.

• DOI: 10.1038/s41467-023-40069-4
• 发表时间: 2023-07-25
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: van Kippersluis, Hans;Biroli, Pietro;Dias Pereira, Rita;Galama, Titus J.;von Hinke, Stephanie;Meddens, S. Fleur W.;Muslimova, Dilnoza;Slob, Eric A. W.;de Vlaming, Ronald;Rietveld, Cornelius A.
• 通讯作者: Rietveld, Cornelius A.