Journal
CIRCULATION-CARDIOVASCULAR GENETICS
Volume 2, Issue 1, Pages 73-U128Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.108.829747
Keywords
epidemiology; meta-analysis; genetics; genomics
Funding
- NIH [N01-AG-12100]
- NIA Intramural Re-search Program, Hjartavernd (the Icelandic Heart Association)
- Althingi (the Icelandic Parliament)
- National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, U01 HL080295, R01 HL087652]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health [HHSN268200625226C, UL1RR025005]
- NIH Roadmap for Medical Research. Cardiovascular Health Study [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133]
- National Institute of Neurological Disorders and Stroke
- National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]
- Affymetrix, Inc [N02-HL-6-4278]
- National Institute of Neurological Disorders and Stroke [NS17950]
- National Institute of Aging [AG08122, AG16495]
- Netherlands Organization of Scientific Research NWO [nr.175.010.2005.011]
- Erasmus Medical Center
- Erasmus University, Rotterdam
- Netherlands Organization for Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
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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. (Circ Cardiovasc Genet. 2009;2:73-80.)
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