Genetic Epidemiology of Causal Variants Across the Life Course

描述(申请人提供)：生命过程中因果变异的遗传流行病学是根据RFA HG-07-014提交的，作为一个以人群为基础的研究联合体和一个中央基因分型和重新测序核心实验室，以促进对与复杂疾病相关的假定因果遗传变异的作用和种群影响的理解。这个合作网络包括六项现有的基于人口统计数据的最具信息量和多样性的研究，贡献了来自美国主要民族和种族群体的约5.8万名男性和女性，年龄从儿童到老年不等。在六项研究中检查的那些被广泛描述为广泛的表型和特征，五项研究立即可以获得储存的高质量的DNA，以便转移到核心实验室。 参与的研究包括重复检查和长期跟踪的基于人群的队列，以及国家概率样本，对一系列健康状况、其前驱疾病和自然病史进行临床和亚临床测量，以表征整个生命过程。这一合作网络旨在提供最佳能力，以便在与公共卫生相关的个人和环境背景下，在不同的美国人口中评估和复制基因变异与复杂疾病的关联，并具有足够的能力来识别关联、相互作用和子组中的人口影响。 研究人员团队提供流行病学、遗传学、方法论和主题方面的专业知识，以及在协作、跨学科环境中证明的生产力记录。该网络建立在汇集的合作伙伴研究的现有能力和经过验证的行政渠道的基础上，以便高效和及时地获取表型、暴露和背景数据，以便在每项合作伙伴研究中进行分析，并在各研究之间复制，以及快速分享由此产生的描述性数据和关联性数据。调查人员将在更广泛的研究中作为有效的合作者，贡献方法创新和分析支持，并在指导委员会设立的委员会和工作组中服务。 在这一应用程序中集合的协作资源将允许估计选定的遗传变异在基于多样性的人群中的作用和对种群的影响，对于一系列慢性病、其风险因素和中间结果，在不同的生命周期，以及对于由潜在可改变的背景所定义的群体。将根据需要进行基因组分析，以进一步确定已报道的相关性。

DESCRIPTION (provided by applicant): Genetic Epidemiology of Causal Variants Across the Life Course is submitted in response to RFA HG-07-014, as a consortium of well characterized population based studies and a central genotyping and resequencing core laboratory, to accelerate the understanding of the role and population impact of putative causal genetic variants related to complex diseases. This collaborative network includes six of the most informative and demographically diverse population-based studies extant, contributing approximately 58,000 men and women from the main ethnic and racial groups in the U.S., ranging in age from childhood to old adulthood. Those examined in the six studies are extensively characterized for a wide range of phenotypes and traits, and five studies have immediately available stored DNA of high quality for transfer to the core laboratory. The participating studies include population based cohorts with repeat examinations and long term follow up and a national probability sample, with clinical and subclinical measurements on a range of health conditions, their precursors and natural history, characterized across the life course. This collaborative network is designed to provide optimal capabilities to estimate and replicate associations of genetic variants with complex diseases in diverse U.S. populations, in individual and environmental contexts of public health relevance, with power sufficient to identify associations, interactions, and population impact in subgroups. The team of investigators contributes epidemiologic, genetic, methodologic and subject-matter expertise and a demonstrated record of productivity in collaborative, interdisciplinary settings. The network builds on existing capabilities and the proven administrative channels of the assembled partner studies for efficient and timely access to phenotypic, exposure and contextual data, for analyses within each partner study and for replication across studies, and for rapid sharing of the resulting descriptive and association data. The investigators will serve as effective collaborators within the wider study, contributing methodologic innovation and analytic support and serving on committees and working groups set up by the Steering Committee. The collaborative resource assembled in this application will permit the estimation of the role and population impact of selected genetic variants in diversity-based populations, for an array of chronic diseases, their risk factors and intermediate outcomes, at different life epochs, and for groups defined by potentially modifiable contexts. Genomic assays will be conducted as needed to further characterize the reported associations.