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.

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 fellowship and travel support for young investigators.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL105756-07
Application #
9584837
Study Section
Cancer, Heart, and Sleep Epidemiology A Study Section (CHSA)
Program Officer
Papanicolaou, George
Project Start
2011-02-15
Project End
2022-06-30
Budget Start
2018-07-15
Budget End
2019-06-30
Support Year
7
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Irvin, Marguerite R; Sitlani, Colleen M; Noordam, Raymond et al. (2018) Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry. Pharmacogenomics J :
Roostaei, Tina; Felsky, Daniel; Nazeri, Arash et al. (2018) Genetic influence of plasma homocysteine on Alzheimer's disease. Neurobiol Aging 62:243.e7-243.e14
Floyd, J S; Sitlani, C M; Avery, C L et al. (2018) Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group. Pharmacogenomics J 18:127-135
Kulminski, Alexander M; Huang, Jian; Loika, Yury et al. (2018) Strong impact of natural-selection-free heterogeneity in genetics of age-related phenotypes. Aging (Albany NY) 10:492-514
Seyerle, A A; Sitlani, C M; Noordam, R et al. (2018) Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology. Pharmacogenomics J 18:215-226
Sung, Yun J (see original citation for additional authors) (2018) A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure. Am J Hum Genet 102:375-400
Mendelian Randomization of Dairy Consumption Working Group (2018) Dairy Consumption and Body Mass Index Among Adults: Mendelian Randomization Analysis of 184802 Individuals from 25 Studies. Clin Chem 64:183-191
Girdhar, Kiran; Hoffman, Gabriel E; Jiang, Yan et al. (2018) Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome. Nat Neurosci 21:1126-1136
Kunutsor, Setor K; Laukkanen, Jari A; Burgess, Stephen (2018) Genetically elevated gamma-glutamyltransferase and Alzheimer's disease. Exp Gerontol 106:61-66
Nordestgaard, Liv Tybjærg; Tybjærg-Hansen, Anne; Rasmussen, Katrine Laura et al. (2018) Genetic variation in clusterin and risk of dementia and ischemic vascular disease in the general population: cohort studies and meta-analyses of 362,338 individuals. BMC Med 16:39

Showing the most recent 10 out of 351 publications