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（如糖尿病和癌症）组织起来，以确定与遗传变异的关联。基因组流行病学心脏和衰老研究队列（CHARGE）联盟的成立是为了促进GWAS对大型人群队列研究中广泛表型的前瞻性荟萃分析，目前包括年龄、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、鹿特丹研究、健康老龄化和身体成分研究、动脉粥样硬化多民族研究、年轻人冠状动脉风险发展研究和杰克逊心脏研究。这些队列研究以标准化的方式收集了危险因素、亚临床疾病和心血管事件的重复测量。这项合作利用了在这些队列研究中投资的数亿美元，代表了识别与各种心血管和衰老表型相关的遗传位点的独特资源。CHARGE是大型复杂研究的自愿联盟，代表了gwas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。自2011年以来，在CHARGE基础设施拨款（HL105756）的资助下，该联盟蓬勃发展。CHARGE主要使用GWAS的250万个snp数据，目前已发表了270多篇论文，其中许多发表在高影响力期刊上。CHARGE队列最近获得或即将获得新的遗传和组学数据：1)GWAS数据，其中58600个数据输入到1000个基因组参考面板的3680万个snp；2) 53,900个ExomeChip上的200,000个罕见变异；3)全外显子组序列数据约26,300；4) 4850份全基因组序列数据；5) 9000条甲基化数据；6)基因表达数据10300；7)代谢组学数据11.66万；8) 6000个的miRNA数据。如果继续支持CHARGE基础设施，40个CHARGE工作组将最有效地使用这些新数据。这个竞争性续期申请的目的是：1)为CHARGE联盟提供类似协调中心的行政支持，包括电话会议、工作组、委员会和会议；2)每年组织2次重大会议；3)为学生、研究员和初级教师提供交流支持，让他们在CHARGE项目的另一个地点工作；4)为偶尔的复制工作提供适度的基因分型资源；5)为每一组学生参与CHARGE提供适度的支持。为了实现这些目标，合作健康研究协调中心（CHSCC）将提供行政支持，Boerwinkle博士和Rotter博士的实验室将作为基因分型中心。通过交流对初级研究人员的支持将促进合作，加强当前的科学，并改善对我们未来科学家的培训。

DESCRIPTION (provided by applicant): Recently, consortia of genome-wide association studies (GWAS) have organized around specific phenotypes such as diabetes and cancer to identify associations with genetic variants. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was formed to facilitate GWAS prospective meta- analyses of a wide range of phenotypes among large population-based cohort studies, now including the Age, Gene/Environment Susceptibility Study, Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, the Rotterdam Study, the Health Aging and Body Composition Study, Multi- Ethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults Study, and the Jackson Heart Study. These cohort studies have repeated measures of risk factors, subclinical disease measures, and cardiovascular events all collected in a standardized fashion. This collaboration, which takes advantage of the hundreds of millions of dollars invested in these cohort studies, represents a unique resource for identifying genetic loci associated with a variety of cardiovascular and aging phenotypes. A voluntary federation of large complex studies, CHARGE represents a major innovation in GWAS-consortium structure because the organizing principle is the cohort study design rather than the phenotype. Since 2011, with funding from the CHARGE infrastructure grant (HL105756), the consortium has thrived. Using primarily GWAS data imputed to 2.5 million SNPs, CHARGE now has more than 270 publications, many in high impact journals. CHARGE cohorts have recently obtained or will soon obtain new genetic and omics data: 1) GWAS data on 58,600 imputed to the 1000 genomes reference panel of 36.8 million SNPs; 2) 200,000 rare variants from the ExomeChip on 53,900; 3) whole-exome sequence data on about 26,300; 4) whole-genome sequence data on 4,850; 5) methylation data on 9000; 6) gene expression data on10,300; 7) metabolomics data on 116,600; and 8) miRNA data on 6,000. The 40 CHARGE Working Groups will use these new data most effectively if there is continued support for the CHARGE infrastructure. The aims of this competing renewal application are: 1) to provide coordinating-center-like administrative support for the CHARGE consortium, including conference calls, working groups, committees, and meetings; 2) to organize 2 major meetings per year; 3) to provide support for exchanges for students, fellows and junior faculty to spend time working at another site on a CHARGE project; 4) to provide modest genotyping resources for occasional replication efforts; and 5) to provide modest support to each cohort for participation in CHARGE. To accomplish these aims, the Collaborative Health Studies Coordinating Center (CHSCC) will provide administrative support and the laboratories of Drs Boerwinkle and Rotter will serve as the genotyping centers. Support for junior investigators with exchanges will foster collaboration, enhance the current science, and improve the training of our future scientists.