Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI
Guillaume Lettre1, Cameron D Palmer, Taylor Young
1Montreal Heart Institute, Montréal, Canada.
Plos Genetics
|February 25, 2011
Summary
Genome-wide association studies in African Americans identified genetic factors for coronary heart disease (CHD) and its risk factors. Distinct linkage disequilibrium patterns revealed stronger associations than previously found in Caucasian populations.
Area of Science:
- Genetics
- Cardiovascular Disease Epidemiology
Background:
- Coronary heart disease (CHD) is a leading cause of mortality in African Americans.
- Genetic factors contributing to CHD disparities in this population remain incompletely understood.
Purpose of the Study:
- To identify common genetic polymorphisms associated with CHD and its risk factors (LDL-C, HDL-C, hypertension, smoking, type-2 diabetes) in African Americans.
- To leverage unique genetic patterns in African ancestry to refine associations with CHD risk factors.
Main Methods:
- Genome-wide association study (GWAS) in 8,090 African Americans across five cohorts.
- Replication of 17 loci previously associated with CHD or risk factors in Caucasians.
- Development of a novel association testing approach for admixed populations using allelic and local ancestry variation.
Main Results:
- Replicated 17 known CHD-associated loci.
- Identified stronger associations for five regions (CDKN2A/CDKN2B, FADS1-3, PLTP, LPL, ABCA1) by utilizing distinct linkage disequilibrium patterns in African Americans.
- Discovered novel loci missed by standard methods using the new ancestry-aware association testing approach.
Conclusions:
- No single major genetic locus uniquely explains the high prevalence of CHD in African Americans.
- Developed valuable resources and methods for genetic discovery in admixed populations, enhancing power for future large-scale consortia.
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