Genetics of coronary artery calcification among African Americans, a meta-analysis

Mary K. Wojczynski, Mingyao Li, Lawrence F. Bielak, Kathleen F. Kerr, Alex P. Reiner, Nathan D. Wong, Lisa R. Yanek, Liming Qu, Charles C. White, Leslie A. Lange, Jane F. Ferguson, Jing He, Taylor Young, Thomas H. Mosley, Jennifer A. Smith, Brian G. Kral, Xiuqing Guo, Quenna Wong, Santhi K. Ganesh, Susan R. HeckbertMichael E. Griswold, Daniel H. O'Leary, Matthew Budoff, J. J. Carr, Herman A. Taylor, David A. Bluemke, Serkalem Demissie, Shih Jen Hwang, Dina N. Paltoo, Joseph F. Polak, Bruce M. Psaty, Diane M. Becker, Michael A. Province, Wendy S. Post, Christopher J. O'Donnell, James G. Wilson, Tamara B. Harris, Maryam Kavousi, L. A. Cupples, Jerome I. Rotter, Myriam Fornage, Lewis C. Becker, Patricia A. Peyser, Ingrid B. Borecki, Muredach P. Reilly

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Background: Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants.Methods: We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with ~2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse-variance weighted meta-analysis on results for 5,823 AA from 8 studies. Heritability was calculated using family studies. The most significant SNPs among AAs were evaluated in European Ancestry (EA) CAC data; conversely, the significance of published SNPs for CAC/CHD in EA was queried within our AA meta-analysis.Results: Heritability of CAC was lower in AA (~30%) than previously reported for EA (~50%). No SNP reached genome wide significance (p < 5E-08). Of 67 SNPs with p < 1E-05 in AA there was no evidence of association in EA CAC data. Four SNPs in regions previously implicated in CAC/CHD (at 9p21 and PHACTR1) in EA reached nominal significance for CAC in AA, with concordant direction. Among AA, rs16905644 (p = 4.08E-05) had the strongest association in the 9p21 region.Conclusions: While we observed substantial heritability for CAC in AA, we failed to identify loci for CAC at genome-wide significant levels despite having adequate power to detect alleles with moderate to large effects. Although suggestive signals in AA were apparent at 9p21 and additional CAC and CAD EA loci, overall the data suggest that even larger samples and an ethnic specific focus will be required for GWAS discoveries for CAC in AA populations.

Original languageEnglish
Article number75
JournalBMC Medical Genetics
Issue number1
StatePublished - Jul 19 2013


  • African-American
  • Atherosclerosis
  • Coronary artery calcium
  • Genetics
  • Meta-analysis


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