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:10270731
- 负责人:
- 金额:$ 25.68万
- 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:ATAC-seqAddressAffectAfrican AmericanAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaAmyloidAreaAstrocytesBiologicalBiological MarkersBiologyBloodBrainCellsCholesterolClinicalClinical TrialsCollaborationsCommunitiesComprehensive Health CareConsensusConsentDNADNA Sequence AlterationDataData AnalysesData SetDementiaDiagnosisDiseaseDisease ProgressionDiverse WorkforceElderlyEligibility DeterminationEndowmentEnrollmentEnsureEthicsExtended FamilyFacultyFamilyFamily history ofFirst Degree RelativeFundingGenesGeneticGenetic CounselingGenetic DiseasesGenetic RiskGenetic VariationGenomicsGenotypeGoalsGrantHeartHeterogeneityHispanic AmericansHispanicsIndividualInflammationInternationalLeadMagnetic Resonance ImagingMedicalMedical GeneticsMethodsMethylationMexican AmericansMicrogliaMitochondriaMotorMultiomic DataMutationNeuronsNeurosciencesNot Hispanic or LatinoNuclear Pore ComplexOffice of Administrative ManagementOligodendrogliaOrganoidsParticipantPathologicPathway interactionsPatientsPharmaceutical PreparationsPhenotypePopulationPopulation HeterogeneityPositron-Emission TomographyPrecision therapeuticsPreventionResearchResearch MethodologyResearch PersonnelResearch SupportResourcesRiskRisk EstimateSamplingScienceSensorySerumSouth TexasSyndromeTrainingTraining ProgramsValidationWorkbiobankcatalystcell typeclinical sequencingcohortdata managementdigitaleducation researchfollow-upfunctional genomicsgenetic associationgenetic variantgenome sequencinggenome wide association studygenomic datagenomic epidemiologygraduate studentimaging biomarkerimprovedindividual patientindividualized preventioninduced pluripotent stem cellinnovationlipidomicsmachine learning methodmembermetabolomicsmultiple omicsneuropathologynew therapeutic targetnormal agingnovelpersonalized medicinephenotypic dataprecision medicineprobandprognosticranpirnaserecruitresiliencerisk stratificationsymposiumtau Proteinstherapeutic targettranscriptomicswhole genome
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.
老年痴呆症在临床、遗传和病理上是异质性的。理解这一
异质性和解决所有增加风险和降低弹性的生物途径,将是
需要提供精确的预防、诊断和治疗。全基因组关联研究(GWAS)
涉及超过40个基因、多个细胞和多种生物学途径(淀粉样蛋白、tau蛋白、内溶酶体,
线粒体功能、炎症)。ADRD在个体中的遗传和多组学特征,
可以利用这种异质性进行更有效、精确、个性化的预防
和痴呆症的治疗。然而,大多数生物学发现都是在非西班牙裔白人身上发现的,
关于墨西哥裔美国人(MA)西班牙裔的数据很少,他们是老年人中增长最快的部分。
美国的成年人。南德克萨斯阿尔茨海默病的遗传学和多组学核心(GMC)
联合会(STAC)有以下具体目标:
目的1:通过以下方法的组合,确定CC入组者中ADRD潜在的因果遗传变异:
常规临床测序和“未诊断疾病网络”方法来识别新的遗传
可能是因果或促成的变化。为了实现这一目标,我们将记录临床测序的结果,
先证者及其亲属的遗传咨询。
目标2:对所有CC入组者进行遗传学表征(使用APOE和GWAS),以扩大我们的研究范围。
了解遗传变异改变风险、复原力和疾病进展。我们将致力于完善
并改善晚发AD、PD、DLB的遗传风险估计,
MA西班牙裔,更好地针对临床试验中的招募。
目标3:作为STAC调查人员、受训人员和国家ADRD研究的资源
社区的深度表型西班牙裔MA样品,基因组数据和创新的分析方法。
为了实现这一目标,(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、代谢组学、脂质组学和感觉运动生物标志物)和数字
和传统的神经病理学,通过NCRAD,NIAGADS,NACC;(ii)GMC将作为STAC
提供甲基化、转录组学(血液、脑、CSF)、ATAC-Seq、单细胞组学数据和
用于产生可用的iPSC和类器官;(iii)GMC将开发和分享创新的遗传和多组学
关联分析方法,特别是在大家庭中使用;(四)GMC将促进与
如阿尔茨海默病遗传学联盟(ADGC)、国际AD基因组学联盟(International Genomics of AD)等。
项目(IGAP),基因组流行病学(CHARGE)和Transomics心脏和衰老研究队列
(五)GMC的教师和资源将支持研究教育核心,
发展一支在应用遗传和多组学研究方法方面训练有素的多样化劳动力队伍。
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)
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Sudha Seshadri其他文献
Sudha Seshadri的其他文献
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{{ truncateString('Sudha Seshadri', 18)}}的其他基金
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:
10472672 - 财政年份:2021
- 资助金额:
$ 25.68万 - 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:
10270724 - 财政年份:2021
- 资助金额:
$ 25.68万 - 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:
10662325 - 财政年份:2021
- 资助金额:
$ 25.68万 - 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:
10662350 - 财政年份:2021
- 资助金额:
$ 25.68万 - 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:
10472638 - 财政年份:2021
- 资助金额:
$ 25.68万 - 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:
9546246 - 财政年份:2018
- 资助金额:
$ 25.68万 - 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:
9222693 - 财政年份:2015
- 资助金额:
$ 25.68万 - 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:
9118841 - 财政年份:2014
- 资助金额:
$ 25.68万 - 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:
8836758 - 财政年份:2014
- 资助金额:
$ 25.68万 - 项目类别:
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:
8579953 - 财政年份:2009
- 资助金额:
$ 25.68万 - 项目类别:
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