CHARGE consortium: omics discovery for CVD and aging phenotypes

全基因组关联研究（GWAS）的联合体经常围绕特定的表型进行组织 例如糖尿病，以发现与遗传变异的关联。相比之下，心脏和衰老的队列研究 基因组流行病学研究（CHARGE）联盟由大型人群队列组成 研究，以促进前瞻性计划的GWAS荟萃分析的广泛的表型。扩大 从最初的5项研究增加到10项，CHARGE队列重复测量了亚临床风险因素， 疾病测量和心血管事件。他们的合作是一种独特的资源， 鉴定和验证与多种心血管和衰老表型相关的遗传基因座。 自2011年以来，HL 105756一直支持CHARGE联盟，该联盟有977篇出版物，其中许多是高质量的， 影响力期刊，超过51，000次引用，h指数为113。近年来，调查人员从 CHARGE队列不仅获得了额外的遗传数据，还获得了全基因组序列（WGS） 54，771名参与者的数据和26，383名参与者的全外显子组序列（WES）数据;以及各种组学 数据，有些在多个时间点，包括1）38，682名参与者的53，780次DNA甲基化检测; 2） 对13，305人进行了17，175次基因表达测定; 3）对34，110人进行了43，660次代谢组学测定;以及4）52，707次 蛋白质组学检测36043. CHARGE及其38个活跃的工作组（WG）， 与NIH项目协调，如NHLBI的TOPMed，能够很好地适应新的 遗传流行病学方向-大规模合作的发现和各种方法的使用 和组学数据来定义功能。新的应用程序是参与百万退伍军人 程序，将CHARGE分析共享资源转换为在NHLBI的BioData Catalyst上运行 生态系统，并增加了CHARGE多基因风险评分，学术生物库和蛋白质组学 WG.这种竞争性更新的目标是加速发现疾病的潜在机制 通过对基因组数据的强大分析， 通过分析方法以及与现有和新兴组学数据的整合来关联变体。的 这种竞争性更新应用程序的目标是：1）提供类似协调中心的行政支持 2）每年组织两次主要会议以及辅助会议; 研讨会; 3）组织每月的网络研讨会; 4）为早期职业生涯提供CHARGE会议旅行奖励 提交最佳摘要的研究人员; 5）为分析共享区提供行政支持 和CHARGE dbGaP总结结果网站;以及6）为参与者提供适度的支持 小组和委员会。对于那些经常支持CHARGE分析的早期职业调查人员来说， 和手稿，CHARGE财团已成为事实上的国际培训基地， 在衰老和心血管疾病遗传学方面的流行病学合作努力。

Consortia of genome-wide association studies (GWAS) have often organized around specific phenotypes such as diabetes to discover associations with genetic variants. In contrast, the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was 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. Their collaboration represents a unique resource for identifying and validating genetic loci associated with a variety of cardiovascular and aging phenotypes. Since 2011, HL105756 has supported the CHARGE consortium, which has 977 publications, many in high- impact journals, more than 51,000 citations, and an h-index of 113. In recent years, investigators from the CHARGE cohorts have obtained not only additional genetic data—both whole-genome sequence (WGS) data on 54,771 participants and whole-exome sequence (WES) data on 26,383; but also a variety of omics data, some at multiple time points, including 1) 53,780 DNA methylation assays on 38,682 participants; 2) 17,175 gene expression assays on 13,305; 3) 43,660 metabolomic assays on 34,110; and 4) 52,707 proteomics assays on 36,043. CHARGE and its 38 active Working Groups (WGs), which collaborate and coordinate with NIH programs such as the NHLBI’s TOPMed, are well positioned to accommodate new directions in genetic epidemiology—large-scale collaborations for discovery and the use of various methods and omics data to define function. New to this application are the participation by the Million Veteran Program, the transition of the CHARGE Analysis Commons to run on the NHLBI’s BioData Catalyst ecosystem, and the addition of the CHARGE Polygenic Risk Scores, Academic Biobank, and Proteomics WGs. The goals of this competing renewal are to accelerate discovery of mechanisms underlying diseases of the cardiovascular system through robust analysis of genomic data and to discover the function of the associated variants through analytic methods and integration with existing and emerging omics data. The aims of this competing renewal application are: 1) to provide coordinating-center-like administrative support for CHARGE, its committees, and WGs; 2) to organize two major meetings per year as well as ancillary workshops; 3) to organize monthly webinars; 4) to provide CHARGE-meeting travel awards for early-career investigators who submit the best abstracts; 5) to provide administrative support for the Analysis Commons and the CHARGE dbGaP Summary Results Website; and 6) to provide modest support for the participating cohorts and committees. For early-career investigators, who have often championed CHARGE analyses and manuscripts, the CHARGE consortium has become a de facto international training ground for collaborative epidemiological efforts in the genetics of aging and CVD.