Genomics Project

基因组计划

基本信息

批准号：
10006788
负责人：
ARPANA AGRAWAL
金额：
$ 200.98万
依托单位：
SUNY DOWNSTATE MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-09-29 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10006788
关键词：
3-Dimensional ATAC-seq Achievement Address Adolescence Affect Alcohol abuse Alcohol consumption Alcohols Architecture Behavioral Biological Biological Assay Biological Specimen Banks Brain CRISPR/Cas technology Cells Chromatin Clinical Collaborations Data Data Set Development Developmental Course Elderly Environment Environmental Risk Factor Family Family member Future Gene Expression Genes Genetic Genetic Predisposition to Disease Genetic study Genomics Goals Healthcare Human Impaired cognition Individual Longevity Measures Meta-Analysis Mission Modality Molecular Multiomic Data National Institute on Alcohol Abuse and Alcoholism Neurobiology Neurocognitive Neurons Neuropsychology Organoids Outcome Parents Pathway interactions Phase Phenotype Population Positioning Attribute Predisposing Factor Prevention Preventive Intervention Public Health Recording of previous events Recovery Relapse Reporter Research Research Personnel Resources Risk Sampling Science Siblings Social Environment Structure Testing Translating Variant adverse outcome alcohol research alcohol use disorder base bench to bedside brain tissue cell type clinical care cognitive development cohort data management data sharing differential expression emerging adulthood epigenomics ethnic diversity genetic variant genetics of alcoholism genome editing genome wide association study genome-wide genomic locus human data improved indexing induced pluripotent stem cell insight longitudinal course member middle age multiple data types neurobehavioral neurophysiology non-genetic offspring population health precision medicine psychiatric genomics relating to nervous system repository resilience response risk variant trait transcriptome transcriptome sequencing transcriptomics

项目摘要

The Collaborative Study on the Genetics of Alcoholism (COGA) is a tightly integrated and interdisciplinary project, whose overarching goals are to understand the contributions and interactions of genetic, neurobiological, and environmental factors on risk and resilience over the developmental course of AUD, including relapse and recovery. COGA is a family-based study of large, ethnically diverse families, some densely affected by AUD, and family members have been characterized in clinical, behavioral, neuropsychological, neurophysiological, and socio-environmental domains, yielding a rich phenotypic dataset paired with a large repository of biospecimens and genomewide SNP data (GWAS) in 12,145 family members. The breadth and depth of longitudinal assessments in COGA families allow genomic analyses to be conducted within a developmental context, allowing inferences regarding genetic susceptibility and environmental malleability, which may contribute to avenues for prevention and intervention. COGA builds on the key strengths of our research achievements over the past 30 years toward our central mission, to understand the genetics of AUD and its interplay with environment. In response to RFA-AA-19-001, we propose three inter-related and inter-dependent projects (Genomics, Brain Function, Lifespan) supported by 3 essential cores (NIAAA-COGA Sharing Repository (NCSR), Data Management, and Administrative). The projects and cores harness the diverse expertise of the COGA team and the close collaboration among COGA investigators resulting in tight integration and progress toward COGA's goals. Consistent with the RFA and in keeping with COGA's research agenda, the overarching specific aims for the next five years are: Aim 1: Characterize loci, genes, polygenic risk and biological pathways underlying alcohol use and AUDs, and identify the genomic and cellular/neuronal signatures that contribute to alcohol-related phenotypes Aim 2: Advance our understanding of the longitudinal course of alcohol use and AUD, and its adverse outcomes by studying genetic and environmental factors across the lifespan Aim 3: Enhance understanding of brain functioning throughout the course of AUD and recovery, and characterize alcohol related cognitive development and decline in the context of genetic and environmental factors. COGA's multi-pronged approach, long history of productive collaboration among the investigators and commitment to data sharing, will allow us to propel the field of alcohol research towards actionable findings that can be positioned to translate science to population health and clinical care. The gestalt that arises from the integration across COGA's research modalities (genomics, brain function, lifespan) is only possible within a U10 mechanism that supports effective collaboration between researchers with diverse toolkits aimed at addressing the serious public health challenge of AUD.

酒精中毒遗传学合作研究 (COGA) 是一项紧密结合的跨学科研究项目，其总体目标是了解遗传、神经生物学、以及环境因素对 AUD 发展过程中风险和复原力的影响，包括复发和恢复。 COGA 是一项以家庭为基础的研究，对象是大型、种族多元化的家庭，其中一些家庭深受澳元的影响，及其家庭成员的临床、行为、神经心理学、神经生理学和社会环境领域，产生丰富的表型数据集以及大型生物样本库以及 12,145 个家庭成员的全基因组 SNP 数据 (GWAS)。纵向宽度和深度 COGA 家族的评估允许在发育背景下进行基因组分析，允许对遗传易感性和环境可塑性进行推断，这可能有助于预防和干预的途径。 COGA 建立在我们过去 30 年研究成果的关键优势之上使命是了解 AUD 的遗传学及其与环境的相互作用。响应 RFA-AA-19-001，我们提出了三个相互关联和相互依赖的项目（基因组学、脑功能、寿命），并得到以下机构的支持 3 个基本核心（NIAAA-COGA 共享存储库 (NCSR)、数据管理和管理）。这项目和核心利用 COGA 团队的多元化专业知识以及 COGA 之间的密切合作调查人员紧密整合并朝着 COGA 的目标取得进展。与 RFA 一致根据 COGA 的研究议程，未来五年的总体具体目标是：目标 1：描述饮酒和 AUD 背后的位点、基因、多基因风险和生物途径，以及识别导致酒精相关表型的基因组和细胞/神经元特征目标 2：加深我们对饮酒和 AUD 的纵向过程及其不良后果的了解通过研究整个生命周期的遗传和环境因素目标 3：在 AUD 和恢复过程中增强对大脑功能的了解，以及在遗传和环境背景下描述与酒精相关的认知发展和衰退因素。 COGA 的多管齐下的方法、研究人员之间富有成效的合作的悠久历史以及对数据共享的承诺将使我们能够推动酒精研究领域取得可操作的发现可以将科学转化为人口健康和临床护理。格式塔产生于 COGA 研究模式（基因组学、脑功能、寿命）的整合只能在 U10 内实现支持研究人员与不同工具包之间有效合作的机制，旨在解决澳元面临的严重公共卫生挑战。