Brain Function Project

酒精中毒遗传学合作研究（COGA）是一个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， 和环境因素对AUD发展过程中的风险和恢复力的影响，包括复发和 复苏COGA是一项以家庭为基础的研究，研究对象是种族多样的大家庭，其中一些家庭深受AUD影响， 和家庭成员的特点是在临床，行为，神经心理，神经生理， 社会环境领域，产生丰富的表型数据集与大型生物标本库配对 和12，145个家族成员的全基因组SNP数据（GWAS）。纵向的宽度和深度 COGA家族的评估允许在发育背景下进行基因组分析， 允许关于遗传易感性和环境可塑性的推断，这可能有助于 预防和干预的途径。 COGA建立在我们过去30年来研究成果的主要优势之上， 使命，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）， 3个基本核心（NIAAA-COGA共享存储库（NCSR）、数据管理和管理）。的 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 调查人员导致紧密的整合和进展COGA的目标。与RFA一致， 根据COGA的研究议程，未来五年的总体具体目标是： 目的1：描述酒精使用和AUDs的基因座、基因、多基因风险和生物学途径， 确定有助于酒精相关表型的基因组和细胞/神经元特征 目的2：提高我们对酒精使用和AUD的纵向过程及其不良后果的理解 通过研究生命周期中的遗传和环境因素， 目标3：加强对AUD和恢复过程中大脑功能的理解， 在遗传和环境背景下描述酒精相关的认知发展和衰退 因素 COGA的多管齐下的方法，调查人员之间富有成效的合作的悠久历史， 致力于数据共享，将使我们能够推动酒精研究领域走向可操作的发现， 可以将科学转化为人口健康和临床护理。产生于 跨COGA的研究模式（基因组学，脑功能，寿命）的整合只有在U10中才有可能 支持研究人员与各种工具包之间有效合作的机制， 澳元面临严重的公共卫生挑战。

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.