CHARGE consortium: gene discovery for CVD and aging phenotypes

全基因组关联研究 (GWAS) 联盟通常围绕特定表型组织起来 例如糖尿病和乳腺癌，以发现与遗传变异的关联。心脏队列 相反，基因组流行病学老龄化研究 (CHARGE) 联盟是由大型组织组成的 基于人群的队列研究，以促进对广泛的前瞻性计划的 GWAS 荟萃分析 表型。 CHARGE 队列从最初的 5 项研究扩大到 10 项，重复测量风险 因素、亚临床疾病测量和心血管事件，全部以标准化方式收集。 他们的合作代表了识别与多种相关的遗传位点的独特资源。 心血管和衰老表型。自 2011 年起，在 CHARGE 基础设施补助金的资助下 （HL105756），该财团蓬勃发展。使用 GWAS 和稀有变异数据，CHARGE 现已发表 数量超过 643 个，其中许多发表在高影响力期刊上。在 NHLBI、NHGRI 和 NIA 的资助下， 许多 CHARGE 队列最近获得了新的遗传和组学数据：1）全基因组 39,819 名受试者的序列 (WGS) 数据； 2) 28,346 条全外显子组序列 (WES) 数据； 3） 16,083 的甲基化数据； 4) 12,133个基因表达数据； 5) 25,521 条代谢组学数据；和 6) 基于适配体的蛋白质组学数据 11,306。 CHARGE 及其 40 个活跃的工作组，相互协作 并与 NIH 项目（例如 NHLBI 的精准医学跨组学项目）进行协调 旨在适应遗传流行病学的所有三个新方向——大规模合作、 基因组序列数据和其他组学数据。此应用程序的新增功能是 CHARGE dbGaP 摘要 用于公开发布摘要结果的结果网站，用于汇总分析的分析共享区 序列数据和组学数据，以及孟德尔随机委员会的分析支持 这些创新方法。这个竞争性更新应用程序的目标是加速发现 通过对基因组数据的稳健分析和心血管系统疾病的潜在机制 通过整合多种形式的大分子来识别发现的变体的功能意义 规模组学数据。这一竞争性续订应用程序的目的是：1）提供类似协调中心的服务 电话会议、工作组、委员会和会议的行政支持； 2）组织两个 每年主要的现场会议； 3) 为提交最佳成绩的新研究者提供旅行奖励 CHARGE 会议上的演示或海报摘要； 4）提供奖学金支持 为学生、研究员和初级教师提供交流，让他们有时间在另一个地点工作，但需付费 项目； 5) 为队列参与提供适度的支持。该联盟推动广泛 合作。对于初级研究人员来说，奖学金交流和旅行奖励也促进了合作， 加强当前的科学，并改善对未来科学家的培训。

Consortia of genome-wide association studies (GWAS) have often organized around specific phenotypes such as diabetes and breast cancer to discover associations with genetic variants. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was instead formed from large- population-based cohort studies to facilitate prospectively-planned GWAS meta-analyses of a wide range of phenotypes. Expanded from the original 5 studies to 10, CHARGE cohorts have repeated measures of risk factors, subclinical disease measures, and cardiovascular events, all collected in a standardized fashion. Their collaboration represents a unique resource for identifying genetic loci associated with a variety of cardiovascular and aging phenotypes. Since 2011, with funding from the CHARGE infrastructure grant (HL105756), the consortium has thrived. Using GWAS and rare-variant data, CHARGE publications now number more than 643, many in high impact journals. With funding from the NHLBI, NHGRI, and the NIA, many of the CHARGE cohorts have recently obtained new genetic and omics data: 1) whole-genome sequence (WGS) data on 39,819 subjects; 2) whole-exome sequence (WES) data on 28,346; 3) methylation data on 16,083; 4) gene expression data on 12,133; 5) metabolomics data on 25,521; and 6) aptamer-based proteomics data on 11,306. CHARGE and its 40 active Working Groups, which collaborate and coordinate with NIH programs such as the NHLBI's Trans-Omics for Precision Medicine, are well positioned to accommodate all three new directions in genetic epidemiology—large-scale collaborations, genomic sequence data, and other omics data. New to this application are the CHARGE dbGaP Summary Results Website for public posting of summary results, the Analysis Commons for pooled analyses of sequence data and omics data, and the Mendelian Randomization Committee for analytic support with these innovative methods. The goals of this competing renewal application are to accelerate discovery of mechanisms underlying diseases of the cardiovascular system through robust analysis of genomic data and to identify the functional significance of the discovered variants through integration of multiple forms of large scale omics data. The aims of this competing renewal application are: 1) to provide coordinating center-like administrative support for conference calls, working groups, committees, and meetings; 2) to organize two major in-person meetings per year; 3) to provide travel awards for new investigators who submit the best abstracts for presentations or posters at the CHARGE meetings; 4) to provide support for fellowship exchanges for students, fellows and junior faculty to spend time working at another site on a CHARGE project; and 5) to provide modest support for cohort participation. The consortium promotes widespread collaboration. For junior investigators, the fellowship exchanges and travel awards also foster collaboration, enhance the current science, and improve the training of our future scientists.