Genome-Wide association study of coronary heart disease and its risk factors in 8,090 african americans: The nhlbi CARe project

Guillaume Lettre, Cameron D. Palmer, Taylor Young, Kenechi G. Ejebe, Hooman Allayee, Emelia J. Benjamin, Franklyn Bennett, Donald W. Bowden, Aravinda Chakravarti, Al Dreisbach, Deborah N. Farlow, Aaron R. Folsom, Myriam Fornage, Terrence Forrester, Ervin Fox, Christopher A. Haiman, Jaana Hartiala, Tamara B. Harris, Stanley L. Hazen, Susan R. HeckbertBrian E. Henderson, Joel N. Hirschhorn, Brendan J. Keating, Stephen B. Kritchevsky, Emma Larkin, Mingyao Li, Megan E. Rudock, Colin A. McKenzie, James B. Meigs, Yang A. Meng, Tom H. Mosley, Anne B. Newman, Christopher H. Newton-Cheh, Dina N. Paltoo, George J. Papanicolaou, Nick Patterson, Wendy S. Post, Bruce M. Psaty, Atif N. Qasim, Liming Qu, Daniel J. Rader, Susan Redline, Muredach P. Reilly, Alexander P. Reiner, Stephen S. Rich, Jerome I. Rotter, Yongmei Liu, Peter Shrader, David S. Siscovick, W. H Wilson Tang, Herman A. Taylor, Russell P. Tracy, Ramachandran S. Vasan, Kevin M. Waters, Rainford Wilks, James G. Wilson, Richard R. Fabsitz, Stacey B. Gabriel, Sekar Kathiresan, Eric Boerwinkle

Research output: Contribution to journalArticlepeer-review

259 Scopus citations


Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1), we could leverage the distinct linkage disequilibrium (LD) patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia.

Original languageEnglish (US)
Article numbere1001300
JournalPLoS genetics
Issue number2
StatePublished - Feb 2011

Bibliographical note

Funding Information:
JBM has a research grant from GSK and a consulting agreement with Interleukin Genetics, SLH reports being listed as co-inventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics. SLH reports having been paid as a consultant or speaker for the following companies: AstraZeneca Pharmaceuticals LP, BG Medicine, Merck & Co., Pfizer Takeda, Esperion, and Cleveland Heart Lab. SLH reports receiving research funds from Abbott, Liposcience, and Cleveland Heart Lab. WHWT reports receiving research grant support from Abbott Laboratories.


Dive into the research topics of 'Genome-Wide association study of coronary heart disease and its risk factors in 8,090 african americans: The nhlbi CARe project'. Together they form a unique fingerprint.

Cite this