Harmonized Diagnostic Assessment of Dementia (DAD) for Longitudinal Aging Study of India (LASI)-Genomic study.

印度纵向衰老研究 (LASI) 基因组研究的痴呆症统一诊断评估 (DAD)。

• 批准号: 10685990
• 负责人: Sharon L Kardia
• 金额: $ 165.2万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10685990
• 关键词: Acceleration; Admixture; Age; Aging; Alzheimer' s Disease; Asian; Asian population; Biological Assay; Brain imaging; Cognition; Cognitive; Cognitive aging; Collaborations; Communities; Conceptions; Country; Data; Dementia; Diagnostic; Dizygotic Twins; Economics; Elderly; Ensure; Episodic memory; European ancestry; Event; Family; Family member; Gene Frequency; Genes; Genetic; Genome; Genomics; Genotype; Goals; Health; Health Care Costs; Health Surveys; Health and Retirement Study; India; Individual; Interview; Life Expectancy; Life Style; Linkage Disequilibrium; Longitudinal Studies; Minor; Molecular; Monozygotic twins; Mutation; Mutation Spectra; Participant; Persons; Phenotype; Pilot Projects; Play; Population; Population Genetics; Protocols documentation; Respondent; Role; Sampling; Social Environment; Social Well-Being; South Asian; Structure; Surveys; Testing; United States; Variant; White Matter Hyperintensity; Work; aged; brain magnetic resonance imaging; cognitive function; cognitive testing; cohort; dementia risk; design; drug development; economic indicator; epidemiology study; fighting; genetic analysis; genetic epidemiology; genetic makeup; genetic variant; genome sequencing; genome wide association study; genome-wide; high risk population; improved; informant; novel therapeutics; prevent; public health relevance; social; southeast Asian; trait; white matter; whole genome

Summary Genetic factors play an important role in Alzheimer's disease (AD), and there is evidence that genes may play a bigger role in cognition as we age. Studies comparing the correlation in traits between identical and fraternal twins suggest 30-60 percent of the variance in episodic memory is related to the genetic makeup of individuals, with the remainder attributed to environmental influences not shared by family members. However, we still know very little about such complicated interplay between genes and lifestyle in onset, progress, and cognitive aging, calling for furthering genetic epidemiologic research to fight AD. Further, the vast majority of work examining the genetics of cognition has been performed in populations of European ancestry. With greater than 1.35 billion people, India is the second largest country in the world with over 4.1 million people estimated to have dementia. However, Indian/South Asian populations are rarely represented in genomic studies of dementia. To fill this gap, we propose to sequence 2,400 individuals from 12 regions of India to better define the mutational spectrum underlying dementia risk in the Longitudinal Aging Study of India (LASI). LASI is a representative, both nationally and at state-level, survey of the Indian population at age 45 or older (N=61,000). The Harmonized Diagnostic Assessment of Dementia for LASI (LASI-DAD) is an in-depth study of late-life cognition and dementia, drawing a sub-sample of 3,000 LASI respondents aged 60 or older and administering the Harmonized Cognitive Assessment Protocol (HCAP) that was designed to harmonize well with ongoing longitudinal studies of aging around the world, including the Health and Retirement Study (HRS) in the United States, and prior studies in India. This rich set of cognitive phenotypes along with brain imaging and a variety of other health and social environment phenotypes collected in this sub-sample will give us a unique opportunity to identify the mutational spectrum underlying risk of dementia and AD in a representative sample of India. In this application, we propose the following specific aims: (1) to perform whole genome sequencing (WGS) and population genetic analyses of 2,400 participants from 12 regions of India surveyed in the LASI- DAD; (2) to evaluate the association between known AD and dementia gene/genetic variants and cognitive function in sequenced LASI-DAD participants; and (3) to disseminate the WGS data as a reference panel for Southeast Asian mutations and develop, pilot, and evaluate a Southeast Asian genotyping chip to ensure proper assay of Southeast Asian mutations.

概括 遗传因素在阿尔茨海默病（AD）中发挥着重要作用，有证据表明基因 随着年龄的增长，它可能在认知中发挥更大的作用。研究比较相同和不同特征之间的相关性 异卵双胞胎表明，情景记忆中 30-60% 的差异与基因构成有关 个人，其余归因于家庭成员不共享的环境影响。然而， 我们对基因和生活方式之间如此复杂的相互作用的发生、进展和发展仍然知之甚少。 认知老化，呼吁进一步开展遗传流行病学研究来对抗 AD。此外，绝大多数 研究认知遗传学的工作已经在欧洲血统人群中进行。和 印度人口超过13.5亿，是世界第二大国家，人口超过410万 估计得了痴呆症。然而，印度/南亚人群在基因组中很少有代表性 痴呆症的研究。 为了填补这一空白，我们建议对来自印度 12 个地区的 2,400 人进行测序，以更好地定义 印度纵向衰老研究 (LASI) 中潜在痴呆风险的突变谱。 LASI 是一种 对 45 岁或以上印度人口进行的全国和州一级代表性调查 （N=61,000）。 LASI 痴呆症统一诊断评估 (LASI-DAD) 是一项深入研究 晚年认知和痴呆症，抽取了 3,000 名 60 岁或以上的 LASI 受访者作为子样本， 管理协调认知评估协议（HCAP），该协议旨在很好地协调 世界各地正在进行的老龄化纵向研究，包括健康与退休研究 (HRS) 在美国进行的研究以及之前在印度的研究。这套丰富的认知表型以及大脑成像 在此子样本中收集的各种其他健康和社会环境表型将为我们提供 识别代表性人群痴呆和 AD 潜在风险突变谱的独特机会 印度的样本。 在此应用中，我们提出以下具体目标：（1）进行全基因组测序 (WGS) 和来自印度 12 个地区的 2,400 名参加 LASI 调查的参与者的群体遗传分析 爸爸; (2) 评估已知的 AD 和痴呆基因/遗传变异与认知之间的关联 在排序的 LASI-DAD 参与者中发挥作用； (3) 传播 WGS 数据作为参考组 东南亚突变并开发、试验和评估东南亚基因分型芯片，以确保 东南亚突变的正确测定。