Abstract
African Americans have the highest rate of mortality due to coronary heart disease (CHD). Although multiple loci have been identified influencing CHD risk in European-Americans using a genome-wide association (GWAS) approach, no GWAS of incident CHD has been reported for African Americans. We performed a GWAS for incident CHD events collected during 19 years of follow-up in 2,905 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. We identified a genome-wide significant SNP (rs1859023, MAF = 31%) located at 7q21 near the PFTK1 gene (HR = 0.57, 95% CI 0.46 to 0.69, p = 1.86×10−08), which replicated in an independent sample of over 8,000 African American women from the Women's Health Initiative (WHI) (HR = 0.81, 95% CI 0.70 to 0.93, p = 0.005). PFTK1 encodes a serine/threonine-protein kinase, PFTAIRE-1, that acts as a cyclin-dependent kinase regulating cell cycle progression and cell proliferation. This is the first finding of incident CHD locus identified by GWAS in African Americans.
Highlights
Coronary heart disease (CHD) is the leading cause of death worldwide [1]
In the United States, African Americans are at high risk for coronary heart disease (CHD)
Environmental and social factors have a role, genetic factors contribute to CHD risk and mortality
Summary
Coronary heart disease (CHD) is the leading cause of death worldwide [1]. In the United States, African Americans are the most vulnerable population with regard to CHD risk factors and mortality. The presence of multiple CHD risk factors is 50% more likely in African Americans than in the population of European ancestry. Hypertension and diabetes are more prevalent and the highest rate of obesity is found in African American women [2] The factors underlying these disparities are not well understood. Genetic factors are known to influence the risk of CHD [4] and population differences in the frequency and effects of these genetic factors likely have a role. Progress in the discovery of susceptibility genes for multiple chronic diseases and their risk factors has been made possible in recent years through genome-wide association studies (GWAS); African Americans were noticeably absent from most of these studies. Three loci reached the pre-specified genomewide significance threshold (p,561028) (Table 2) and were considered for replication in a sample of African American women from WHI.
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