Genetic Epidemiology of Causal Variants Across the Life Course

描述（由申请方提供）：作为一个充分表征的基于人群的研究联盟和一个中心基因分型和重测序核心实验室，提交了对RFA HG-07-014的响应，以加速理解与复杂疾病相关的推定因果遗传变异的作用和人群影响。这个合作网络包括六个现存的最翔实和人口统计学上最多样化的基于人口的研究，来自美国主要民族和种族群体的大约58，000名男性和女性，年龄范围从童年到老年。在六项研究中检查的那些被广泛表征为广泛的表型和性状，并且五项研究具有立即可用的高质量存储DNA以转移到核心实验室。 参与的研究包括重复检查和长期随访的基于人群的队列和国家概率样本，对一系列健康状况、其前兆和自然史进行临床和亚临床测量，并在整个生命过程中进行表征。该协作网络旨在提供最佳能力，以估计和复制遗传变异与不同美国人群中复杂疾病的关联，在公共卫生相关的个人和环境背景下，具有足以识别关联，相互作用和亚组中的人群影响的能力。 研究人员团队贡献了流行病学，遗传学，方法学和主题的专业知识，以及在协作，跨学科环境中的生产力的证明记录。该网络建立在现有的能力和经过验证的管理渠道的组合合作伙伴的研究，有效和及时地访问表型，暴露和背景数据，分析每个合作伙伴的研究和研究之间的复制，并快速共享所产生的描述性和关联数据。研究人员将在更广泛的研究中担任有效的合作者，促进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任职。 在此应用程序中组装的协作资源将允许在基于多样性的人群中估计选定的遗传变异的作用和人口影响，用于一系列慢性疾病，其风险因素和中间结果，在不同的生命时期，以及由潜在可修改的背景定义的群体。将根据需要进行基因组测定，以进一步表征报告的相关性。

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.