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: 10017825
• 负责人: Sharon L Kardia
• 金额: $ 350.35万
• 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/10017825
• 关键词: Admixture; Age; Aging; Alzheimer' s Disease; Asians; Biological Assay; Brain; Brain imaging; Cognition; Cognitive; Cognitive aging; Communities; Conceptions; Country; Data; Dementia; Diagnostic; Dizygotic Twins; Elderly; Ensure; Episodic memory; European; 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; Lead; Life Expectancy; Life Style; Linkage Disequilibrium; Longitudinal Studies; Magnetic Resonance Imaging; Minor; Molecular; Monozygotic twins; Mutation; Mutation Spectra; Participant; 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; base; cognitive function; cognitive testing; cohort; dementia risk; design; drug development; economic indicator; epidemiology study; fighting; genetic analysis; genetic makeup; genetic variant; genome sequencing; genome wide association study; genome-wide; health economics; high risk; 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氏病（AD）中起重要作用，有证据表明基因 随着年龄的增长，可能在认知中发挥更大的作用。研究比较了相同和相同性状的相关性 兄弟双胞胎表明，情节记忆的差异的30-60％与 个人，其余的归因于家庭成员未分享的环境影响。然而， 我们仍然对基因与生活方式之间的如此复杂的相互作用知之甚少 认知衰老，呼吁进一步促进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的人群中进行。和 印度大于13.5亿人，是世界第二大国家，有超过410万人 估计患有痴呆症。但是，印度/南亚人群很少在基因组中代表 痴呆研究。 为了填补这一空白，我们建议对印度12个地区的2400个人进行排序，以更好地定义 印度纵向老化研究（LASI）中的痴呆症风险的突变谱。拉西是一个 在国家和州级的代表，对印度人口45岁或以上的印度人口调查 （n = 61,000）。 LASI（LASI-DAD）痴呆症的统一诊断评估是对 晚年认知和痴呆 管理旨在很好地统一的统一认知评估协议（HCAP） 随着世界各地衰老的纵向研究，包括健康和退休研究（HRS） 在美国以及印度的先前研究。这套丰富的认知表型以及脑成像 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 在代表中识别痴呆症和AD的突变频谱的独特机会 印度样本。 在此应用中，我们提出以下特定目的：（1）执行整个基因组测序 （WGS）和来自印度12个地区的2,400名参与者的人口遗传分析在Lasi-eworge中进行了调查 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 在测序的LASI-DAD参与者中发挥作用； （3）将WGS数据作为参考面板传播 东南亚突变并开发，试行和评估东南亚基因分型芯片，以确保 适当的东南亚突变分析。