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.

Public Health Relevance

The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium has helped to accelerate the discovery of genetic variants associated with common diseases and risk factors. The proposed application will provide infrastructure support for the consortium, including for instance administrative support for day-to-day activities, the organization of two CHARGE-wide meetings per year, and support for CHARGE fellowships for young investigators to visit another site to advance a CHARGE project.

National Institute of Health (NIH)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Papanicolaou, George
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University of Washington
Internal Medicine/Medicine
Schools of Medicine
United States
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Kauwe, John S K; Bailey, Matthew H; Ridge, Perry G et al. (2014) Genome-wide association study of CSF levels of 59 alzheimer's disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation. PLoS Genet 10:e1004758
Postmus, Iris; Trompet, Stella; Deshmukh, Harshal A et al. (2014) Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. Nat Commun 5:5068
Guan, Weihua; Steffen, Brian T; Lemaitre, Rozenn N et al. (2014) Genome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium. Circ Cardiovasc Genet 7:321-31
Lin, Honghuang; Sinner, Moritz F; Brody, Jennifer A et al. (2014) Targeted sequencing in candidate genes for atrial fibrillation: the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Targeted Sequencing Study. Heart Rhythm 11:452-7
Sinner, Moritz F; Tucker, Nathan R; Lunetta, Kathryn L et al. (2014) Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation. Circulation 130:1225-35
Bis, Joshua C; White, Charles C; Franceschini, Nora et al. (2014) Sequencing of 2 subclinical atherosclerosis candidate regions in 3669 individuals: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study. Circ Cardiovasc Genet 7:359-64
Malik, Rainer; Bevan, Steve; Nalls, Michael A et al. (2014) Multilocus genetic risk score associates with ischemic stroke in case-control and prospective cohort studies. Stroke 45:394-402
Restrepo, Nicole A; Spencer, Kylee L; Goodloe, Robert et al. (2014) Genetic determinants of age-related macular degeneration in diverse populations from the PAGE study. Invest Ophthalmol Vis Sci 55:6839-50
Cornes, Belinda K; Brody, Jennifer A; Nikpoor, Naghmeh et al. (2014) Association of levels of fasting glucose and insulin with rare variants at the chromosome 11p11.2-MADD locus: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study. Circ Cardiovasc Genet 7:374-82
Liu, Ching-Ti; Young, Kristin L; Brody, Jennifer A et al. (2014) Sequence variation in TMEM18 in association with body mass index: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study. Circ Cardiovasc Genet 7:344-9

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