South Texas Alzheimer's Disease Center Genetics and Multiomics Core
南德克萨斯阿尔茨海默病中心遗传学和多组学核心
基本信息
- 批准号:10472672
- 负责人:
- 金额:$ 24.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Dementia in older adults is clinically, genetically and pathologically heterogeneous. Understanding this
heterogeneity and addressing all the biological pathways that increase risk and lower resilience, will be
required to provide precision prevention, diagnosis and treatment. Genome wide association studies (GWAS)
have implicated over 40 genes, multiple cell and varied biological pathways (amyloid, tau, endolysosomal,
mitochondrial function, inflammation). Genetic and multiomic characterization of ADRD in individuals, and in
groups of patients, could exploit this heterogeneity towards more effective, precise, personalized prevention
and treatment of dementia. Whereas, most of these biological discoveries have been in non-Hispanic whites,
there is a paucity of data on Mexican American (MA) Hispanics, who are the fastest growing segment of older
adults in the US. The Genetics and Multiomics Core (GMC) of the South Texas Alzheimer Disease
Consortium (STAC) has the following specific aims:
Aim 1: Identifying causal genetic variation underlying ADRD in CC enrollees through a combination of
routine clinical sequencing and a ‘Undiagnosed Disease Network’ approach to identifying novel genetic
variation that may be causal or contributory. To achieve this, we will record results of clinical sequencing and
genetic counseling in proband and relatives.
Aim 2: Genetically characterize all CC enrollees (using APOE and GWAS) to expand our
understanding of genetic variation modifying risk, resilience and disease progression. We will aim to refine
and improve genetic risk estimates for late onset AD, PD, DLB permitting more accurate risk stratification in
MA Hispanics, better targeting for recruitment in clinical trials.
Aim 3: Serve as a resource for STAC investigators, trainees, and the national ADRD research
community for deeply phenotyped Hispanic MA samples, genomic data and innovative analysis methods.
To achieve this (i) GMC will share DNA, genetic and phenotypic data (clinical, MRI and PET imaging,
blood and CSF -amyloid, tau, inflammation, metabolomic, lipidomic- and sensory-motor biomarkers) and digital
and conventional neuropathology, through NCRAD, NIAGADS, NACC; (ii) GMC will serve as a STAC
resource for providing methylation, transcriptomics (blood, brain, CSF), ATAC-Seq, single-cell omics data and
for generating usable iPSCs and organoids; (iii) GMC will develop and share innovative genetic and multiomic
association analyses methods, especially for use in large families; (iv) GMC will facilitate collaborations with
consortia such as the Alzheimer Disease Genetics Consortium (ADGC), the International Genomics of AD
Project (IGAP), Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and Transomics
in Precision Medicine (TOPMed); (v) GMC faculty and resources will support the Research Education Core in
developing a diverse workforce, well-trained in applying genetic and multiomic research methods.
老年人的痴呆在临床,遗传和病理上是异质的。了解这一点
异质性并解决所有增加风险和降低弹性的生物学途径,将是
需要提供精确预防,诊断和治疗。基因组广泛的关联研究(GWAS)
已经实施了40多个基因,多个细胞和多样的生物途径(淀粉样蛋白,tau,内溶性,
线粒体功能,炎症)。个体中ADRD的遗传和多态表征
一组患者可以利用这种异质性来更有效,精确,个性化的预防
和痴呆症的治疗。鉴于,大多数这些生物学发现都在非西班牙裔白人中
关于墨西哥裔美国人(MA)西班牙裔的数据很少,他们是增长最快的年龄段
美国的成年人。南德克萨斯州阿尔茨海默氏病的遗传学和多组学核心(GMC)
财团(STAC)具有以下具体目标:
AIM 1:通过组合CC中识别CC中基础ADRD的因果遗传变异
常规临床测序和“未诊断疾病网络”的方法来识别新的遗传
可能是因果或贡献的变异。为此,我们将记录临床测序的结果和
概率和亲戚的遗传咨询。
AIM 2:遗传表征所有CC注册(使用APOE和GWAS)扩展我们的
了解遗传变异改变风险,弹性和疾病进展。我们的目标是完善
并改善发作AD,PD,DLB的遗传风险估计值,允许更准确的风险分层
MA西班牙裔,更好地针对临床试验招募。
目标3:作为Stac调查人员,培训和国家ADRD研究的资源
深层表型西班牙裔MA样本,基因组数据和创新分析方法的社区。
为此,(i)GMC将共享DNA,遗传和表型数据(临床,MRI和PET成像,
血液和CSF - 淀粉样蛋白,tau,炎症,代谢组,脂肪组和感觉运动生物标志物)和数字
和常规的神经病理学,通过NACC Niagads,NACC; (ii)GMC将用作Stac
提供甲基化,转录组学(血液,大脑,CSF),ATAC-SEQ,单细胞OMICS数据和
生成可用的IPSC和类器官; (iii)GMC将开发和共享创新的遗传和多组分
协会分析方法,尤其是用于大家庭的使用; (iv)GMC将促进与
财团,例如阿尔茨海默氏病遗传学财团(ADGC),AD的国际基因组学
项目(IGAP),基因组流行病学(电荷)和跨性别的心脏和衰老研究队列
精密医学(顶部); (v)GMC教师和资源将支持研究教育核心
开发潜水员劳动力,在采用遗传和多层研究方法方面进行了良好的训练。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

暂无数据
数据更新时间:2024-06-01
Sudha Seshadri的其他基金
South Texas Alzheimer's Disease Center Administrative Core
南德克萨斯阿尔茨海默病中心行政核心
- 批准号:1027072410270724
- 财政年份:2021
- 资助金额:$ 24.3万$ 24.3万
- 项目类别:
South Texas Alzheimer's Disease Center Genetics and Multiomics Core
南德克萨斯阿尔茨海默病中心遗传学和多组学核心
- 批准号:1027073110270731
- 财政年份:2021
- 资助金额:$ 24.3万$ 24.3万
- 项目类别:
South Texas Alzheimer's Disease Center Administrative Core
南德克萨斯阿尔茨海默病中心行政核心
- 批准号:1066232510662325
- 财政年份:2021
- 资助金额:$ 24.3万$ 24.3万
- 项目类别:
South Texas Alzheimer's Disease Center Genetics and Multiomics Core
南德克萨斯阿尔茨海默病中心遗传学和多组学核心
- 批准号:1066235010662350
- 财政年份:2021
- 资助金额:$ 24.3万$ 24.3万
- 项目类别:
South Texas Alzheimer's Disease Center Administrative Core
南德克萨斯阿尔茨海默病中心行政核心
- 批准号:1047263810472638
- 财政年份:2021
- 资助金额:$ 24.3万$ 24.3万
- 项目类别:
Cognitively Healthy Nonagenarians in the Cross Cohort Collaboration (CCC)
跨队列合作 (CCC) 中认知健康的九十多岁老人
- 批准号:95462469546246
- 财政年份:2018
- 资助金额:$ 24.3万$ 24.3万
- 项目类别:
Preclinical AD: Correlates of Amyloid, Tau PET and fcMRI in Framingham Gen 3 Young Adults
临床前 AD:弗雷明汉第 3 代年轻人中淀粉样蛋白、Tau PET 和 fcMRI 的相关性
- 批准号:92226939222693
- 财政年份:2015
- 资助金额:$ 24.3万$ 24.3万
- 项目类别:
CHARGE: Identifying Risk & Protective SNV for AD in ADSP Case-control Sample
职责:识别风险
- 批准号:91188419118841
- 财政年份:2014
- 资助金额:$ 24.3万$ 24.3万
- 项目类别:
CHARGE: Identifying Risk & Protective SNV for AD in ADSP Case-control Sample
职责:识别风险
- 批准号:88367588836758
- 财政年份:2014
- 资助金额:$ 24.3万$ 24.3万
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AD Gene Discovery: Exome Chip, New Endophenotypes & Functional Studies in CHARGE
AD 基因发现:外显子组芯片、新内表型
- 批准号:85799538579953
- 财政年份:2009
- 资助金额:$ 24.3万$ 24.3万
- 项目类别:
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