CHARGE consortium: gene discovery for CVD and aging phenotypes

描述（由申请人提供）：最近，全基因组关联研究联盟（GWAS）围绕特定表型（如2型糖尿病和脂质）形成，以确定与遗传变异的关联。相比之下，基因组流行病学心脏和衰老研究队列（CHARGE）联盟成立于2008年2月，旨在促进GWAS对大型人群队列研究中广泛表型的前瞻性荟萃分析，包括年龄、基因/环境易感性研究、社区动脉粥样硬化风险研究、心血管健康研究、弗雷明汉心脏研究和鹿特丹研究。健康老龄化与身体成分研究、多民族动脉粥样硬化研究和年轻人冠状动脉风险发展研究也正在参与。这些队列研究有53,000多名参与者，以标准化的方式收集了全基因组数据和风险因素、亚临床疾病测量和心血管事件的重复测量。CHARGE合作项目利用了已经投资于这些队列研究的数亿美元，代表了联盟结构的重大创新，因为组织原则是队列研究设计而不是表型。在短短一年半的合作中，CHARGE研究人员发表或出版了21篇论文，14篇论文正在审查中，还有大约50篇其他分析或论文正在进行中。CHARGE联盟代表了一个没有资金的大型复杂研究自愿联盟，缺乏基础设施支持来维持其日益复杂的运作。没有任何一个群组能够持续提供的两个功能是：1)行政协调中心式的支持，为工作组、委员会、电话会议、会议、跟踪出版物以及网站和wiki的升级提供支持；2)编辑和审稿人通常需要的后续和复制工作的适度基因分型资源。在拟议的R01中，我们不仅计划提供协调中心的支持和适度的基因分型资源，还计划为学生、研究员和初级研究者提供支持，包括为来自一个站点的初级研究者提供在另一个站点花时间工作的新机会（交流）。初级研究人员经常在CHARGE分析和手稿中发挥主导作用，结果CHARGE联盟已经成为一种事实上的国际培训基地，在衰老和心血管疾病的遗传学方面进行合作流行病学努力。所有CHARGE论文都有初级研究人员，这些研究人员被确定为与第一作者同等贡献。CHARGE荟萃分析论文的第一作者通常是博士生（n=4）、博士后（n=2）或初级研究者（n=5）。对学生和初级研究人员的支持以及对队列间交流的支持将促进合作，加强现有科学，并改善对未来科学家的培训。

DESCRIPTION (provided by applicant): Recently, consortia of genome-wide association studies (GWAS) have formed around specific phenotypes such as type 2 diabetes and lipids to identify associations with genetic variants. In contrast, the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was formed in Feb 2008 to facilitate GWAS prospective meta-analyses of a wide range of phenotypes among large population-based cohort studies, including the Age, Gene/Environment Susceptibility Study, Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and the Rotterdam Study. The Health Aging and Body Composition Study, Multi-Ethnic Study of Atherosclerosis, and Coronary Artery Risk Development in Young Adults Study are now participating as well. With more than 53,000 participants, these cohort studies have both genome-wide data and repeated measures of risk factors, subclinical disease measures, and cardiovascular events all collected in a standardized fashion. The CHARGE collaboration, which takes advantage of the hundreds of millions of dollars already invested in these cohort studies, represents a major innovation in consortium structure because the organizing principle is the cohort study design rather than the phenotype. In just over a year and a half of collaboration, the CHARGE investigators have 21 papers published or in press, 14 papers under review, and about 50 other analyses or papers in progress. The CHARGE consortium represents an unfunded voluntary federation of large complex studies, one that lacks infra-structural support to sustain its increasingly complex operations. The two functions that none of the cohorts can offer in a sustained way are: 1) administrative Coordinating-Center-like support for working groups, committees, conference calls, meetings, tracking publications, and upgrades to the website and wiki; and 2) modest genotyping resources for follow-up and replication efforts often required by editors and reviewers. In the proposed R01, we plan to provide not only Coordinating-Center support and modest genotyping resources, but also support for students, fellows and junior investigators, including new opportunities for junior investigators from one site to spend time working at another site (exchanges). Junior investigators have often taken a leading role in CHARGE analyses and manuscripts with the result that the CHARGE consortium has become a kind of de facto international training ground for collaborative epidemiological efforts in the genetics of aging and cardiovascular disease. All CHARGE papers have junior investigators among the set of investigators identified as contributing equally as first authors. First-first authors of CHARGE meta-analysis papers have frequently been doctoral students (n=4), post-doctoral fellows (n=2), or junior investigators (n=5). Support for students and junior investigators and support for between-cohort exchanges will foster collaboration, enhance the current science, and improve the training of our future scientists.