CHARGE consortium: gene discovery for CVD and aging phenotypes

CHARGE 联盟：CVD 和衰老表型的基因发现

• 批准号: 9001355
• 负责人: Bruce M Psaty
• 金额: $ 66.86万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9001355
• 关键词: Aging; Atherosclerosis; Body Composition; Cardiovascular Diseases; Cardiovascular system; Cohort Studies; Collaborations; Communities; Complex; Coronary Artery Risk Development in Young Adults Study; Data; Diabetes Mellitus; Disease; Environment; Epidemiology; Event; Faculty; Fellowship; Fostering; Framingham Heart Study; Funding; Future; Gene Expression; Genetic; Genomics; Genotype; Grant; Health; Heart; Incentives; International; Jackson Heart Study; Journals; Laboratories; Malignant Neoplasms; Manuscripts; Measures; Meta-Analysis; Methylation; MicroRNAs; Minority; Phenotype; Predisposition; Publications; Research; Research Design; Research Infrastructure; Research Personnel; Resources; Risk; Risk Factors; Role; Sample Size; Science; Scientist; Site; Structure; Students; Testing; Texas; Time; Training; Universities; Visit; Work; aging gene; cardiovascular health; cohort; disorder risk; exome sequencing; follow-up; gene discovery; genetic variant; genome sequencing; genome wide association study; improved; innovation; meetings; metabolomics; population based; prospective; rare variant; reference genome; symposium; web site; whole genome; wiki; working group

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.

描述（由申请人提供）：最近，全基因组关联研究（GWAS）联盟已经围绕特定表型（如糖尿病和癌症）组织起来，以确定与遗传变异的关联。基因组流行病学中心脏和衰老研究队列（CHARGE）联盟的形成是为了促进GWAS在基于大人群的队列研究中对广泛表型的前瞻性Meta分析，现在包括年龄、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、鹿特丹研究、健康衰老和身体成分研究、动脉粥样硬化的多种族研究，年轻成人冠状动脉风险发展研究和杰克逊心脏研究。这些队列研究重复测量了危险因素、亚临床疾病指标和心血管事件，所有这些都以标准化的方式收集。这项合作利用了在这些队列研究中投入的数亿美元，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。作为大型复杂研究的自愿联合会，CHARGE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基础设施赠款（HL 105756）的资助下，该财团蓬勃发展。CHARGE主要使用估算到250万个SNP的GWAS数据，目前拥有270多篇出版物，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学和组学数据：1）58，600个GWAS数据，估算到3680万个SNP的1000个基因组参考面板; 2）53，900个ExomeChip的200，000个罕见变异; 3）约26，300个全外显子组序列数据; 4）4，850个全基因组序列数据; 5）9000例的甲基化数据; 6）10,300例的基因表达数据; 7）116,600例的代谢组学数据; 8）6000例的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。这一竞争性更新申请的目的是：1）为CHARGE财团提供协调中心般的行政支持，包括电话会议，工作组，委员会和会议; 2）每年组织2次大型会议; 3）为学生，研究员和初级教师提供交流支持，以便在另一个网站上花费时间在CHARGE项目上工作; 4）为偶尔的复制工作提供适度的基因分型资源; 5）为参与CHARGE的每个队列提供适度的支持。为了实现这些目标，协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。通过交流支持初级研究人员将促进合作，加强当前的科学，并改善我们未来科学家的培训。