Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

TLDR

Genome‑wide association studies aim to identify novel loci linked to variation in risk factors, subclinical disease, and clinical outcomes, and their success depends on large sample sizes and replication, driving scientific collaboration. The CHARGE Consortium unites five large, harmonized cohort studies—Age, Gene/Environment Susceptibility—Reykjavik, Atherosclerosis Risk in Communities, Cardiovascular Health, Framingham, and Rotterdam—providing ~38,000 participants and many phenotypes, and performs within‑cohort GWAS combined by meta‑analysis to robustly detect genetic associations. CHARGE and its collaborators offer an effective framework for discovering genetic determinants of risk factors, subclinical disease measures, and clinical events.

Abstract

Background— The primary aim of genome-wide association studies is to identify novel genetic loci associated with interindividual variation in the levels of risk factors, the degree of subclinical disease, or the risk of clinical disease. The requirement for large sample sizes and the importance of replication have served as powerful incentives for scientific collaboration. Methods— The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium was formed to facilitate genome-wide association studies meta-analyses and replication opportunities among multiple large population-based cohort studies, which collect data in a standardized fashion and represent the preferred method for estimating disease incidence. The design of the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium includes 5 prospective cohort studies from the United States and Europe: the Age, Gene/Environment Susceptibility—Reykjavik Study, the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. With genome-wide data on a total of about 38 000 individuals, these cohort studies have a large number of health-related phenotypes measured in similar ways. For each harmonized trait, within-cohort genome-wide association study analyses are combined by meta-analysis. A prospective meta-analysis of data from all 5 cohorts, with a properly selected level of genome-wide statistical significance, is a powerful approach to finding genuine phenotypic associations with novel genetic loci. Conclusions— The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and collaborating non-member studies or consortia provide an excellent framework for the identification of the genetic determinants of risk factors, subclinical-disease measures, and clinical events.