Genomics Project

基因组计划

• 批准号: 10238792
• 负责人: ARPANA AGRAWAL
• 金额: $ 220.43万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 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/10238792
• 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; Induced pluripotent stem cell derived neurons; Intervention; 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; 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; 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; Induced pluripotent stem cell derived neurons; Intervention; 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; 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

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.

关于酒精中毒遗传学（COGA）的合作研究是一项紧密整合和跨学科的 项目的总体目标是了解遗传，神经生物学， 以及关于AUD发展过程中风险和弹性的环境因素，包括复发和 恢复。 COGA是一项基于家庭的研究，对大型种族多样化的家庭，有些受AUD的密集影响， 和家庭成员在临床，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与大型生物测量库配对 以及12,145个家庭成员的全基因组SNP数据（GWAS）。纵向的宽度和深度 COGA家族的评估允许在发育环境中进行基因组分析， 允许推断遗传易感性和环境可延展性，这可能有助于 预防和干预的途径。 COGA在过去30年中我们的研究成就的关键优势建立在我们的中央 使命，了解AUD及其与环境的相互作用的遗传学。响应RFA-AA-19-001， 我们提出了三个相互关联和相互依存的项目（基因组学，大脑功能，寿命），由 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团队的各种专业知识以及COGA之间的密切合作 调查人员导致了紧密的整合并朝着COGA的目标迈进。与RFA和IN一致 符合COGA的研究议程，未来五年的总体具体目标是： AIM 1：表征基因座，基因，多基因风险和酒精使用和AUD的生物途径，以及 确定有助于酒精相关表型的基因组和细胞/神经元特征 目标2：促进我们对酒精使用和aud的纵向过程的理解及其不利的结果 通过研究整个生命周期的遗传和环境因素 目标3：在整个aud和恢复过程中增强对大脑功能的理解，以及 特征与酒精相关的认知发展和遗传和环境背景下的下降 因素。 COGA的多管齐下方法，研究人员和 致力于数据共享的承诺，将使我们能够将酒精研究领域推向可行的发现， 可以将科学转化为人口健康和临床护理。由 COGA研究方式（基因组学，大脑功能，寿命）之间的整合仅在U10中才有可能 支持具有不同工具包的研究人员之间有效合作的机制，旨在解决 AUD的严重公共卫生挑战。