@article{ece623eee0af4d8caf6c213459a5d9d2,
title = "Genetics of coronary artery calcification among African Americans, a meta-analysis",
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.",
keywords = "African-American, Atherosclerosis, Coronary artery calcium, Genetics, Meta-analysis",
author = "Wojczynski, {Mary K.} and Mingyao Li and Bielak, {Lawrence F.} and Kerr, {Kathleen F.} and Reiner, {Alex P.} and Wong, {Nathan D.} and Yanek, {Lisa R.} and Liming Qu and White, {Charles C.} and Lange, {Leslie A.} and Ferguson, {Jane F.} and Jing He and Taylor Young and Mosley, {Thomas H.} and Smith, {Jennifer A.} and Kral, {Brian G.} and Xiuqing Guo and Quenna Wong and Ganesh, {Santhi K.} and Heckbert, {Susan R.} and Griswold, {Michael E.} and O'Leary, {Daniel H.} and Matthew Budoff and Carr, {J. J.} and Taylor, {Herman A.} and Bluemke, {David A.} and Serkalem Demissie and Hwang, {Shih Jen} and Paltoo, {Dina N.} and Polak, {Joseph F.} and Psaty, {Bruce M.} and Becker, {Diane M.} and Province, {Michael A.} and Post, {Wendy S.} and O'Donnell, {Christopher J.} and Wilson, {James G.} and Harris, {Tamara B.} and Maryam Kavousi and Cupples, {L. A.} and Rotter, {Jerome I.} and Myriam Fornage and Becker, {Lewis C.} and Peyser, {Patricia A.} and Borecki, {Ingrid B.} and Reilly, {Muredach P.}",
note = "Funding Information: The National Heart, Lung, and Blood Institute{\textquoteright}s Family Heart Study (FamHS) was supported by NIH grants R01-HL-087700 and R01-HL-088215 (Michael A. Province, PI) from NHLBI; and R01-DK-8925601 and R01-DK-075681 (Ingrid B. Borecki, PI) from NIDDK. The authors from the CARe Consortium wish to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff and study participants in creating this resource for biomedical research. The following studies have contributed parent study data, ancillary study data, and DNA samples through the Broad Institute (N01-HC-65226). Coronary Artery Risk in Young Adults (CARDIA): University of Alabama at Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California, Irvine (N01-HC-45134, N01-HC-95100); Jackson Heart Study (JHS): Jackson State University (N01-HC-95170), University of Mississippi (N01-HC-95171), Tougaloo College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis (MESA): University of Washington (N01-HC-95159),Regents of the University of California (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162, N01-HC-95168), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Harbor-UCLA Research and Education Institute (N01-HC-95169), Cedars-Sinai Medical Center (R01-HL-071205), University of Virginia (subcontract to R01-HL-071205). The Coronary Artery Risk Development in Young Adults (CARDIA) study is funded by contracts N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, and N01-HC-45204 from the National Heart, Lung, and Blood Institute to the CARDIA investigators. GWAS genotyping and quality control for the CARDIA African-Americans was supported by the NHLBI{\textquoteright}s Candidate-gene Association REsource (CARe) Study. Statistical analysis of CARDIA data was supported by grants R01-HL084099 and U01-HG004729 to MF. This manuscript has been reviewed by CARDIA for scientific content and consistency of data interpretation with previous CARDIA publications. The MESA Family/Air Studies were conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) and the United States Environmental Protection Agency (EPA) in collaboration with MESA Family and MESA Air investigators, respectively. Support for MESA Family is provided by grants and contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, and R01HL071259. Support for MESA Air is provided by grant RD83169701. Funding for genotyping was provided by NHLBI Contract N02-HL-6-4278. Genotyping was performed at the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) and at Affymetrix (Santa Clara, California, USA) using the Affymetrix Genome-Wide Human SNP Array 6.0. The GeneSTAR Study was supported by the National Heart, Lung, and Blood Institute (NHLBI) through the STAMPEED (R01 HL087698-01) consortium as well as grants HL58625-01A1, HL59684, and HL071025-01A1, and a grant from the NIH/National Institute of Nursing Research (NR008153-01). Additional support was provided by a grant from the NIH/National Center for Research Resources (M01-RR000052) to the Johns Hopkins General Clinical Research Center. The Genetic Epidemiology Network of Arteriopathy (GENOA) is supported by the National Institutes of Health, grant numbers HL085571, HL087660, and HL100245 from National Heart, Lung, Blood Institute. We thank Eric Boerwinkle, PhD from the Human Genetics Center and Institute of Molecular Medicine and Division of Epidemiology, University of Texas Health Science Center, Houston, Texas, USA and Julie Cunningham, PhD from the Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA for their help with genotyping. MPR is supported by R01-DK071224, R01-DK-090505, U01-HL108636, K24-HL107643 and R01-HL113147. MK is supported by the AXA Research Fund.",
year = "2013",
month = jul,
day = "19",
doi = "10.1186/1471-2350-14-75",
language = "English (US)",
volume = "14",
journal = "BMC medical genetics",
issn = "1471-2350",
publisher = "BioMed Central",
number = "1",
}