CHARGE consortium: omics discovery for CVD and aging phenotypes

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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.