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

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  • Wojczynski, Mary K
    • Other Affiliation: Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
  • Li, Mingyao
    • Other Affiliation: Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA
  • Bielak, Lawrence F
    • Other Affiliation: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
  • Kerr, Kathleen F
    • Other Affiliation: Department of Biostatistics, University of Washington, Seattle, WA, USA
  • Reiner, Alex P
    • Other Affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA
  • Wong, Nathan D
    • Other Affiliation: Heart Disease Prevention Program, University of California, Irvine, CA, USA
  • Yanek, Lisa R
    • Other Affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • Qu, Liming
    • Other Affiliation: Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA
  • White, Charles C
    • Other Affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
  • Lange, Leslie
    • Affiliation: School of Medicine, Department of Genetics
  • Ferguson, Jane F
    • Other Affiliation: The Cardiovascular Institute and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • He, Jing
    • Other Affiliation: Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA
  • Young, Taylor
    • Other Affiliation: Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
  • Mosley, Thomas H
    • Other Affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
  • Smith, Jennifer A
    • Other Affiliation: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
  • Kral, Brian G
    • Other Affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • Guo, Xiuqing
    • Other Affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
  • Wong, Quenna
    • Other Affiliation: Department of Biostatistics, University of Washington, Seattle, WA, USA
  • Ganesh, Santhi K
    • Other Affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
  • Heckbert, Susan R
    • Other Affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA
  • Griswold, Michael E
    • Other Affiliation: Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS, USA
  • O’Leary, Daniel H
    • Other Affiliation: Department of Radiology, Tufts University School of Medicine, Boston, MA, USA
  • Budoff, Matthew
    • Other Affiliation: University of California Los Angeles School of Medicine, Los Angeles, CA, USA
  • Carr, J
    • Other Affiliation: Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  • Taylor, Herman A
    • Other Affiliation: Jackson State University, Tougaloo College, Jackson, MS, USA; The University of Mississippi Medical Center, Jackson, MS, USA
  • Bluemke, David A
    • Other Affiliation: Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, MD, USA
  • Demissie, Serkalem
    • Other Affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
  • Hwang, Shih-Jen
    • Other Affiliation: National Heart, Lung, and Blood Institute’s Framingham Heart Study and the Center for Population Studies, Framingham, MA, USA
  • Paltoo, Dina N
    • Other Affiliation: Advanced Technologies and Surgery Branch, Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
  • Polak, Joseph F
    • Other Affiliation: Department of Radiology, Tufts University School of Medicine, Boston, MA, USA
  • Psaty, Bruce M
    • Other Affiliation: Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Service, University of Washington, Seattle, WA, USA; Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA
  • Becker, Diane M
    • Other Affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • Province, Michael A
    • Other Affiliation: Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
  • Post, Wendy S
    • Other Affiliation: Departments of Epidemiology and Medicine, The Johns Hopkins School of Medicine and Public Health, Baltimore, MD, USA
  • O’Donnell, Christopher J
    • Other Affiliation: National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, USA; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; National Heart, Lung, and Blood Institute, Bethesda, MD, USA
  • Wilson, James G
    • Other Affiliation: Department of Physiology and Biophysics, University of Mississippi, Jackson, MS, USA
  • Harris, Tamara B
    • Other Affiliation: Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
  • Kavousi, Maryam
    • Other Affiliation: Netherlands Genomics-Initiative-Sponsored Netherlands Consortium for Healthy Aging, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
  • Cupples, L
    • Other Affiliation: National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
  • Rotter, Jerome I
    • Other Affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
  • Fornage, Myriam
    • Other Affiliation: Houston Institute of Molecular Medicine, University of Texas, Houston, TX, USA
  • Becker, Lewis C
    • Other Affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • Peyser, Patricia A
    • Other Affiliation: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
  • Borecki, Ingrid B
    • Other Affiliation: Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
  • Reilly, Muredach P
    • Other Affiliation: The Cardiovascular Institute and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Abstract
  • Abstract 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.
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  • Article
Rights statement
  • In Copyright
Rights holder
  • Mary K Wojczynski et al.; licensee BioMed Central Ltd.
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Journal title
  • BMC Medical Genetics
Journal volume
  • 14
Journal issue
  • 1
Page start
  • 75
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1471-2350
Bibliographic citation
  • BMC Medical Genetics. 2013 Jul 19;14(1):75
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • July 16, 2016

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