Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD): Epigenomic Assays

印度纵向衰老研究痴呆症统一诊断评估 (LASI-DAD)：表观基因组分析

• 批准号: 10848802
• 负责人: Jinkook Lee
• 金额: $ 152.44万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10848802
• 关键词: Acceleration; Age; Aging; Aliquot; Alzheimer' s Disease; Alzheimer' s disease related dementia; Biological; Biological Assay; Biological Markers; Blood; Blood specimen; Calibration; Chronology; Code; Cognition; Cognitive aging; Collection; Communities; Complex; Country; DNA; DNA Methylation; DNA Modification Process; Data; Dementia; Diagnostic; Diet Habits; Dimensions; Disease; Edetic Acid; Environment; Environmental Pollutants; Environmental Risk Factor; Epigenetic Process; European ancestry; Foundations; Funding; Future; Genetic; Genetic Risk; Genomics; Geography; Health and Retirement Study; Health behavior; Impaired cognition; India; Individual; International; Laboratories; Longitudinal Studies; Longitudinal cohort study; Low income; Measurement; Measures; Mediating; Mediator; Methylation; Michigan; Minnesota; Nature; Northern Ireland; Participant; Phase; Population; Privacy; Reporting; Research; Research Design; Research Personnel; Resources; Risk Factors; Sampling; Secure; Security; Site; Sorting; South Asian; Testing; Time; Tube; Universities; Variant; Venous; Venous blood sampling; Work; bead chip; cognitive function; endophenotype; epigenome; epigenome-wide association studies; epigenomics; ethnic difference; genetic variant; genome sequencing; geographic difference; interest; population based; social; social stressor; socioeconomics; virtual; whole genome

Summary Epigenetic modifications of DNA, such as DNA methylation, have been strongly associated with chronological age and can be used to estimate age acceleration in individuals. Epigenetic factors may also mediate or modify the effects of AD-related genetic variants. Given the dynamic nature of epigenome and many influencing factors (both environmental and genetic), longitudinal studies that measure methylation at multiple timepoints are being increasingly recognized as the most suitable approach to analyze the epigenetics of complex diseases. However, longitudinal studies to estimate change in epigenetics are very limited anywhere in the world and are virtually non-existent in population-based representative samples. Furthermore, little work has been done on epigenetics and AD and cognitive function in lower income, non-Western countries. To fill this gap, we aim to measure longitudinal epigenomic variation in the Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) in DNA samples that are already extracted (Wave 1) and venous blood samples currently being collected (Wave 2). This work will enable essential studies of the epigenetic predictors of aging, cognitive impairment, and Alzheimer’s disease and related dementias (ADRD) in South Asians from India, as well as the study of epigenetic mediators and modifiers of genetic risk for cognitive impairment and dementia. Moreover, since epigenomic variation often reflects environmental variation with risk factors that have been associated with AD (e.g., environmental pollutants, socioeconomic and social stressors, health behaviors, and dietary habits), it is critical to evaluate potential biological mechanisms by which these social, environmental, and individual risk factors may influence disease in South Asian and other non-Western populations, including how they change over time. In this application, we propose the following specific aims: (1) to simultaneously conduct epigenomic assays for longitudinal study by first extracting DNA from the Wave 1 VBS (1a), sorting and pairing wave 1 and wave 2 samples and preparing plates for methylation assays (1b), and conducting epigenomic assays for paired samples (DNAs extracted for the same individuals at two different timepoints, 5-years apart) using the Infinium Methylation EPIC 2 BeadChip; (2) to conduct a cross-laboratory calibration study for future cross-country comparisons, particularly with the Health and Retirement Study (HRS) and its international network of studies.

概括 DNA 的表观遗传修饰，例如 DNA 甲基化，与时间顺序密切相关 年龄，可用于估计个体的年龄加速，表观遗传因素也可能介导或改变。 鉴于表观基因组的动态性质和许多影响因素，AD 相关遗传变异的影响。 （环境和遗传），测量多个时间点甲基化的纵向研究正在进行中 越来越多地被认为是分析复杂疾病的表观遗传学的最合适的方法。 世界上任何地方估计表观遗传学变化的研究都非常有限，而且几乎是纵向的 此外，在表观遗传学方面的工作很少。 低收入非西方国家的 AD 和认知功能。 为了填补这一空白，我们的目标是测量协调诊断中的纵向表观基因组变异 印度纵向老化研究 (LASI-DAD) 的 DNA 样本中的痴呆症评估 提取的（第 1 波）和目前正在采集的静脉血样本（第 2 波）这项工作将实现必要的功能。 衰老、认知障碍和阿尔茨海默病及相关疾病的表观遗传预测因子的研究 印度南亚人痴呆症（ADRD）的研究，以及表观遗传调节因子和修饰因子的研究 此外，由于表观基因组变异通常反映了损伤和痴呆的遗传风险。 环境变化以及与 AD 相关的风险因素（例如环境污染物、 （就业和社会压力源、健康行为和饮食习惯），评估潜力至关重要 这些社会、环境和个人风险因素可能影响疾病的生物学机制 南亚和其他非西方人群的情况，包括他们如何随时间变化。 在此应用中，我们提出以下具体目标：（1）同时进行表观基因组分析 用于纵向研究，首先从第 1 波 VBS (1a) 中提取 DNA，对第 1 波和第 2 波进行排序和配对 样品和准备甲基化板 (1b)，并对配对测定样品进行表观基因组测定 （在相隔 5 年的两个不同时间点为同一个体提取 DNA）使用 Infinium 甲基化 EPIC 2 BeadChip；(2) 进行跨实验室校准研究以进行未来的跨国比较， 特别是健康与退休研究 (HRS) 及其国际研究网络。