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

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

• 批准号: 10836795
• 负责人: Sharon L Kardia
• 金额: $ 38.64万
• 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/10836795
• 关键词: 2019-nCoV; Admixture; Age; Aging; Altitude; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Architecture; Asia; Asian population; California; Cognition; Cognitive; Data Set; Dementia; Diagnostic; East Asian; European; Future; Genes; Genetic; Genetic Variation; Genome; Genomics; Genotype; Geographic Locations; Haplotypes; Health; Human; India; Individual; Linguistics; Link; Maps; Methods; Michigan; Modernization; Parents; Phenotype; Play; Population; Positioning Attribute; Postdoctoral Fellow; Recording of previous events; Research Personnel; Role; Sampling; Shapes; Skin Pigmentation; South Asian; Surveys; Universities; Variant; Work; experience; genomic data; insight; large datasets; public health relevance; recruit; response; trait; 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. Our preliminary analysis of the whole genome sequences from LASI-DAD shows that our study has the most comprehensive survey of genetic variation in South Asia. Further, we have uncovered that like most non-Africans, South Asians have ~1-3% ancestry from archaic hominins––Neanderthals and Denisovans. Surveys of Eurasians have shown that this history has played a critical role in shaping the genetic and phenotypic variation in modern humans. For instance, archaic ancestry in Eurasians has impacted numerous traits ranging from skin pigmentation to high altitude adaptation, and response to SARS-CoV-2. However, most studies have focused on Europeans and East Asians, with very few genomes from other parts of the world. Further, no study has investigated the role of archaic ancestry in impacting the risk of Alzheimer’s disease or cognitive phenotypes. To fill this gap, we aim to investigate how archaic hominins (Neanderthal and Denisovan) ancestry impacts the risk of Alzheimer’s disease and cognitive phenotypes in modern humans using the large dataset of 2,700 samples from our LASI-DAD study. The LASI-DAD dataset contains 2,700 individuals from diverse ethnolinguistic groups in India, with extensive phenotype information for Alzheimer’s disease risk and cognitive phenotypes. The detailed genotype and phenotype information from the LASI-DAD dataset provides a unique opportunity to study the impact of Neanderthal, Denisovan and introgressed segments from other unknown hominins on the health of present-day individuals and uncover introgressed genes associated with Alzheimer's disease risk. Moreover, we are currently collecting more samples from additional regions and the study is a very timely project as we can collect more samples from specific groups to increase our power for genotype-phenotype analysis that show promising results. In this application, we propose the following specific aims: (1) to generate a map of archai introgression in modern humans; (2) to perform association analysis to study the association of Alzheimer’s disease risk and archaic ancestry; (3) to recruit samples from additional regions to maximize its potential for future population genomics study.

摘要 遗传因素在阿尔茨海默病(AD)中起着重要作用，有证据表明 随着年龄的增长，基因可能会在认知方面发挥更大的作用。我们对整体的初步分析 来自LASI-DAD的基因组序列表明，我们的研究拥有最全面的 南亚的遗传变异。此外，我们还发现，像大多数非非洲人一样，南非 亚洲人有大约1-3%的远古人类祖先--尼安德特人和丹尼索瓦人。调查： 欧亚人已经表明，这段历史在塑造人类的基因和 现代人的表型变异。例如，欧亚大陆的古老祖先影响了 从皮肤色素沉着到高原适应的众多特征，以及对 SARS-CoV-2。然而，大多数研究都集中在欧洲人和东亚人身上，很少有 来自世界其他地区的基因组。此外，还没有研究调查古生词的作用 影响阿尔茨海默病风险或认知表型的祖先。 为了填补这一空白，我们的目标是研究古人类(尼安德特人和丹尼索万人)如何 血统影响现代人患阿尔茨海默病的风险和认知表型 使用来自LASI-DAD研究的2700个样本的大型数据集。LASI-DAD数据集 包含来自印度不同民族语言群体的2700人，具有广泛的表型 有关阿尔茨海默病风险和认知表型的信息。详细的基因分型和 来自LASI-DAD数据集的表型信息为研究 尼安德特人、丹尼索瓦人和其他未知人种的导入片段对人类的影响 现代个体的健康和发现与阿尔茨海默氏症相关的导入基因 疾病风险。此外，我们目前正从更多地区收集更多样本， 研究是一个非常及时的项目，因为我们可以从特定的群体中收集更多的样本来增加我们的 显示出有希望的结果的基因型-表型分析的能力。 在本申请中，我们提出了以下具体目标：(1)生成古生物地图 (2)进行关联分析，研究人与人的关系 阿尔茨海默氏症的风险和古老的祖先；(3)从更多地区招募样本以 最大限度地发挥其在未来群体基因组学研究中的潜力。

项目成果

Cohort Profile: Real-Time Insights of COVID-19 in India (RTI COVID-India).

• DOI: 10.1186/s12889-023-15084-1
• 发表时间: 2023-02-09
• 期刊: BMC public health
• 影响因子: 4.5