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（GWAS）联盟围绕特定表型（如2型糖尿病和血脂）形成，以确定与遗传变异的关联。相比之下，2008年2月成立了基因组流行病学心脏和衰老研究队列（CHARGE）联盟，以促进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、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，以及年轻人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，包括全基因组数据和风险因素的重复测量，亚临床疾病测量和心血管事件，所有这些都以标准化的方式收集。CHARGE合作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篇正在审查的论文，以及大约50篇正在进行的其他分析或论文。CHARGE联盟是一个没有资金支持的大型复杂研究的自愿联合会，缺乏基础设施支持来维持其日益复杂的运作。没有一个群组能够以持续的方式提供两个功能：1）行政协调中心式的支持，用于工作组，委员会，电话会议，会议，跟踪出版物，以及网站和wiki的升级; 2）编辑和评审员经常需要的后续和复制工作的适度基因分型资源。在拟议的R 01中，我们计划不仅提供协调中心支持和适度的基因分型资源，还为学生、研究员和初级研究人员提供支持，包括为来自一个研究中心的初级研究人员提供在另一个研究中心工作的新机会（交流）。初级研究人员经常在CHARGE分析和手稿中发挥主导作用，其结果是CHARGE联盟已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流行病学合作。所有的CHARGE论文都有初级研究人员，他们被认为是第一作者。CHARGE荟萃分析论文的第一作者通常是博士生（n=4）、博士后研究员（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，增强当前的科学，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状况相关的遗传变异。这些发现可能会导致对疾病过程，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.