CHARGE consortium: gene discovery for CVD and aging phenotypes

描述(由申请人提供)：最近，围绕特定的表型，如2型糖尿病和血脂，形成了全基因组关联研究联盟，以确定与遗传变异的关联。与之形成鲜明对比的是，心脏与衰老基因组流行病学研究(CHARD)联盟于2008年2月成立，旨在促进对大型人群队列研究中各种表型的前瞻性荟萃分析，这些研究包括年龄、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、Framingham心脏病研究和鹿特丹研究。健康老龄化和身体成分研究，动脉粥样硬化的多种族研究，以及青年冠状动脉风险发展研究现在也参与其中。这些队列研究有超过53,000名参与者，既有全基因组数据，也有风险因素、亚临床疾病测量和心血管事件的重复测量，所有这些都是以标准化的方式收集的。Charge协作利用了已经在这些队列研究上投入的数亿美元，代表了联合体结构的一项重大创新，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，指控调查人员已发表或正在印刷的论文有21篇，正在审查的论文有14篇，其他大约50篇分析或论文正在进行中。Charge财团代表着一个没有资金的大型复杂研究的自愿联盟，缺乏基础设施支持来维持其日益复杂的运营。没有一个群体能够持续提供的两项功能是：1)为工作组、委员会、电话会议、会议、跟踪出版物以及网站和维基的升级提供行政协调中心式的支持；以及2)编辑和审查者经常需要的用于后续和复制工作的适度的基因分型资源。在拟议的R01中，我们计划不仅提供协调中心的支持和适度的基因鉴定资源，而且还为学生、研究员和初级调查人员提供支持，包括为一个地点的初级调查人员提供新的机会，让他们在另一个地点(交流)工作。初级调查人员经常在指控分析和手稿中发挥主导作用，结果是指控联盟已成为衰老和心血管疾病遗传学方面合作流行病学努力的一种事实上的国际培训场所。所有指控文件的调查人员中都有初级调查人员，他们的贡献与第一作者相同。CARGE Meta分析论文的第一作者经常是博士生(n=4)、博士后研究员(n=2)或初级研究员(n=5)。对学生和初级研究人员的支持以及对队列之间交流的支持将促进合作，加强当前的科学，并改善我们未来科学家的培训。 公共卫生相关性：拟议的项目将有助于发现与各种心血管和衰老疾病相关的基因变异。这一发现可能会导致对一种疾病的过程、预防和治疗的新理解。

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. PUBLIC HEALTH RELEVANCE: The proposed project will assist in the discovery of genetic variants associated with a variety of cardiovascular and aging conditions. The findings may lead to a new understanding about a disease processes, prevention and treatment.