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Prospective Associations of Coronary Heart Disease Loci in African Americans Using the MetaboChip: The PAGE Study

Prospective Associations of Coronary Heart Disease Loci in African Americans Using the MetaboChip: The PAGE Study
BackgroundCoronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans.Methods and ResultsUp to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex- and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P = 8.1×10−8), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium.ConclusionsOur findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.
- Johns Hopkins University United States
- Harvard University United States
- Emory University United States
- Rutgers, The State University of New Jersey United States
- National Institute of Health Pakistan
Male, Epidemiology, Science, Cardiology, 610, Coronary Disease, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-myc, Medicine and Health Sciences, Coronary Heart Disease, Humans, Genetic Predisposition to Disease, Prospective Studies, Cardiovascular Disease Epidemiology, Genetic Association Studies, Oligonucleotide Array Sequence Analysis, Q, R, Black or African American, Adaptor Proteins, Vesicular Transport, Cardiovascular Diseases, Genetic Epidemiology, Medicine, Female, Research Article
Male, Epidemiology, Science, Cardiology, 610, Coronary Disease, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-myc, Medicine and Health Sciences, Coronary Heart Disease, Humans, Genetic Predisposition to Disease, Prospective Studies, Cardiovascular Disease Epidemiology, Genetic Association Studies, Oligonucleotide Array Sequence Analysis, Q, R, Black or African American, Adaptor Proteins, Vesicular Transport, Cardiovascular Diseases, Genetic Epidemiology, Medicine, Female, Research Article
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