Genome-Wide Association Analysis of Incident Coronary Heart Disease (CHD) in African Americans: A Short Report

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 perfor...

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Published in:	PLoS genetics Vol. 7; no. 8; p. e1002199
Main Authors:	Barbalic, Maja, Reiner, Alex P., Wu, Chunyuan, Hixson, James E., Franceschini, Nora, Eaton, Charles B., Heiss, Gerardo, Couper, David, Mosley, Thomas, Boerwinkle, Eric
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 01.08.2011 Public Library of Science (PLoS)
Subjects:	African Americans Aged Biology Black or African American - genetics Cardiovascular disease Coronary Disease - ethnology Coronary Disease - genetics Coronary heart disease Female Gene expression Gene Expression Regulation Genetic aspects Genetic Loci - genetics Genome-Wide Association Study Genomes Health aspects Heart attacks Humans Kinases Male Medicine Middle Aged Mortality Polymorphism, Single Nucleotide - genetics Risk Factors Womens health United States
ISSN:	1553-7404, 1553-7390, 1553-7404
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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.
AbstractList	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. 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. 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 x [10.sup.-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. 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.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. 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. In the United States, African Americans are at high risk for coronary heart disease (CHD). Although environmental and social factors have a role, genetic factors also contribute to CHD risk and mortality. Research to identify genetic factors for CHD susceptibility has been carried out mostly in Europeans and European Americans and little has been done in African Americans. Genome wide association studies (GWAS) provide a means to identify susceptibility loci without any a priori assumptions about the functional importance of a gene. In this study, we used GWAS to identify a novel genomic region associated with incident CHD events in African Americans from the ARIC study and replicated this finding in a large sample of African American women. This region contains several genes, including PFTK1, that regulate cell cycle progression and cell proliferation. This is the first report of a susceptibility locus for incident CHD identified by GWAS in African Americans.
Audience	Academic
Author	Boerwinkle, Eric Hixson, James E. Franceschini, Nora Mosley, Thomas Heiss, Gerardo Couper, David Barbalic, Maja Reiner, Alex P. Eaton, Charles B. Wu, Chunyuan
AuthorAffiliation	5 Center for Primary Care and Prevention, Alpert Medical School, Brown University, Providence, Rhode Island, United States of America 3 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America 2 Department of Epidemiology, University of Washington, Seattle, Washington, United States of America 7 Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States of America 1 Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, United States of America 4 Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, United States of America 6 Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, United States of America Georgia Institute of Technology, United States of America
AuthorAffiliation_xml	– name: 3 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America – name: 7 Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States of America – name: 6 Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, United States of America – name: 1 Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, United States of America – name: 5 Center for Primary Care and Prevention, Alpert Medical School, Brown University, Providence, Rhode Island, United States of America – name: 4 Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, United States of America – name: Georgia Institute of Technology, United States of America – name: 2 Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: MB APR EB. Analyzed the data: MB APR CW. Contributed reagents/materials/analysis tools: APR JEH CBE GH DC TM EB. Wrote the paper: MB APR EB NF.
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Snippet	African Americans have the highest rate of mortality due to coronary heart disease (CHD). Although multiple loci have been identified influencing CHD risk in... African Americans have the highest rate of mortality due to coronary heart disease (CHD). Although multiple loci have been identified influencing CHD risk in...
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SubjectTerms	African Americans Aged Biology Black or African American - genetics Cardiovascular disease Coronary Disease - ethnology Coronary Disease - genetics Coronary heart disease Female Gene expression Gene Expression Regulation Genetic aspects Genetic Loci - genetics Genome-Wide Association Study Genomes Health aspects Heart attacks Humans Kinases Male Medicine Middle Aged Mortality Polymorphism, Single Nucleotide - genetics Risk Factors Womens health
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Title	Genome-Wide Association Analysis of Incident Coronary Heart Disease (CHD) in African Americans: A Short Report
URI	https://www.ncbi.nlm.nih.gov/pubmed/21829389 https://www.proquest.com/docview/883007602 https://pubmed.ncbi.nlm.nih.gov/PMC3150445 https://doaj.org/article/3c9cddcb26044d5782a30ec7d896daa7 http://dx.doi.org/10.1371/journal.pgen.1002199
Volume	7
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