Genomics Core

基因组学核心

• 批准号: 10264233
• 负责人: VIVIANNA M VAN DEERLIN
• 金额: $ 27.1万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10264233
• 关键词: Advisory Committees; African American; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid; Autopsy; Bioinformatics; Biological; Biological Markers; Blood; Brain; C9ORF72; Cerebrovascular Disorders; Chronology; Clinical; Clinical Trials; Cohort Studies; Collaborations; Collection; Communities; Complex; Counseling; DNA; DNA Methylation; DNA-Binding Proteins; Data; Databases; Deposition; Disease; Doctor of Philosophy; Education; Ensure; Epigenetic Process; Faculty; Family; Family member; Funding; Genes; Genetic; Genetic Counseling; Genome; Genomics; Genotype; Goals; Hereditary Disease; Heterogeneity; Individual; Inherited; Longevity; Measurement; Measures; Mission; Mutation; Nerve Degeneration; Neurodegenerative Disorders; Nucleic Acids; Onset of illness; Participant; Pathogenicity; Pathologic; Pathology; Patients; Pennsylvania; Play; Population; Population Heterogeneity; Process; Quality Control; Recording of previous events; Research; Research Personnel; Resistance; Resources; Risk; Role; Sampling; Scientist; Services; Severity of illness; Training; Trans-Omics for Precision Medicine; Universities; Variant; aging brain; alpha synuclein; biobank; brain tissue; career; cohort; data management; data sharing; disease heterogeneity; disorder risk; education research; epigenetic marker; exome; familial Alzheimer disease; genetic analysis; genetic association; genetic counselor; genetic variant; genome-wide; improved; innovation; member; neuroimaging; neuropathology; novel therapeutics; outreach; polygenic risk score; presenilin-1; recruit; resilience; segregation; tau Proteins; trait

GENOMICS CORE SUMMARY Core Leader: Vivianna M. Van Deerlin, MD, PhD; Core Co-leader: Corey T. McMillan, PhD The focus of the University of Pennsylvania (Penn) Alzheimer’s Disease Research Center (ADRC) is to develop a mechanistic understanding of the still evolving complexity of Alzheimer disease (AD) and related dementias (ADRD) by studying the spectrum of disease from earliest onset through progressive stages of disease and ultimately at autopsy. Aside from rare and highly penetrant mutations that cause familial AD, several genetic factors play a critical role for risk of AD/ADRD. Also, epigenetic markers change throughout the lifespan and may contribute to AD heterogeneity by potentially providing resistance to pathology or resilience to clinical progression. The Genetics Core was first funded in 2017 to meet the Penn ADRC’s growing needs of increasing the genetic characterization of the Penn ADRC Cohort and here we propose to transition from traditional genetics to a Genomics Core. The Genomics Core will innovatively incorporate genetics and bioinformatics expertise with the goal of supporting the Penn ADRC mission by providing resources to conduct and support genomics research in collaboration with the other cores through the following Aims: (1) Extract nucleic acid from biosamples for biobanking and sharing; (2) Perform genotyping and generate polygenic risk scores to relate to pathology and downstream processes of AD; (3) Measure DNA methylation and generate epigenetic summary scores like “epigenetic clock”; (4) Screen and counsel patients for hereditary disease; and (5) Enhance diversity in research and education of genetics of AD. We will accomplish these Aims by receiving DNA from Clinical Core subjects through the Biomarker and Neuropathology Cores. DNA banking efforts will be enhanced by the diversity of subjects in the Penn Aging Brain Cohort (ABC) Study that is enriched for African Americans and the collaborating Aging Brain Cohort Dedicated to Diversity (ABCD2). We will closely collaborate with the Data Management and Statistic (DMS) Core to deposit resulting data into the Integrated Neurodegenerative Disease Database. This will enable collaborating Penn ADRC Cores, and through data sharing initiatives other internal and external investigators, to perform genetic association studies of neuroimaging, biofluid biomarkers and clinical progression with the goal of improving our understanding of the complexities and heterogeneity of AD/ADRD and identifying mechanistic candidates for novel therapies. Through these activities we will additionally contribute to the Research and Education Component (REC) by training early career scientists including fellows and junior faculty.

基因组学核心摘要 核心领导者：Vivianna M. Van Deerlin，医学博士、哲学博士；核心联合领导者：Corey T. McMillan 博士 宾夕法尼亚大学 (Penn) 阿尔茨海默病研究中心 (ADRC) 的重点是 对阿尔茨海默病（AD）及相关疾病仍在不断发展的复杂性形成机制理解 痴呆症（ADRD），通过研究从最早发病到进展阶段的疾病谱 疾病并最终进行尸检。除了导致家族性 AD 的罕见且高渗透性突变之外， 一些遗传因素对 AD/ADRD 风险起着关键作用。此外，表观遗传标记在整个过程中都会发生变化 寿命，并可能通过潜在地提供对病理或恢复的抵抗力来促进 AD 异质性 至临床进展。遗传学核心于 2017 年首次获得资助，以满足宾夕法尼亚州 ADRC 不断增长的需求 增加 Penn ADRC 队列的遗传特征，在这里我们建议从 传统遗传学到基因组学核心。基因组学核心将创新性地将遗传学和 生物信息学专业知识，目标是通过提供资源来支持宾夕法尼亚大学 ADRC 使命 并通过以下目标与其他核心合作支持基因组学研究：（1）提取 生物样本中的核酸用于生物库和共享； (2) 进行基因分型并产生多基因风险 与 AD 病理学和下游过程相关的分数； (3) 测量DNA甲基化并生成 表观遗传总结分数，如“表观遗传时钟”； （4）对患者进行遗传性疾病筛查和咨询；和 (5) 增强AD遗传学研究和教育的多样性。我们将通过以下方式实现这些目标 通过生物标记和神经病理学核心接收临床核心受试者的 DNA。 DNA银行 宾夕法尼亚大学老龄脑队列（ABC）研究中受试者的多样性将加强努力，该研究是 为非裔美国人和致力于多样性的老龄化大脑队列 (ABCD2) 进行了丰富的内容。 我们将与数据管理和统计（DMS）核心密切合作，将结果数据存入 综合神经退行性疾病数据库。这将使 Penn ADRC 核心能够协作，并且 通过数据共享计划与其他内部和外部研究人员进行遗传关联研究 神经影像学、生物流体生物标志物和临床进展的研究，目的是提高我们对 AD/ADRD 的复杂性和异质性，并确定新疗法的候选机制。 通过这些活动，我们还将为研究和教育部分（REC）做出贡献： 培训早期职业科学家，包括研究员和初级教师。