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 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 Becker, Patricia A. Peyser, Ingrid B. Borecki, Muredach P. Reilly

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number75
JournalBMC Medical Genetics
Volume14
Issue number1
DOIs
StatePublished - Jul 19 2013

Fingerprint

African Americans
Meta-Analysis
Coronary Vessels
Single Nucleotide Polymorphism
Coronary Disease
Genome
Genome-Wide Association Study
Cause of Death
Alleles

Keywords

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

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Wojczynski, M. K., Li, M., Bielak, L. F., Kerr, K. F., Reiner, A. P., Wong, N. D., ... Reilly, M. P. (2013). Genetics of coronary artery calcification among African Americans, a meta-analysis. BMC Medical Genetics, 14(1), [75]. https://doi.org/10.1186/1471-2350-14-75

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

In: BMC Medical Genetics, Vol. 14, No. 1, 75, 19.07.2013.

Research output: Contribution to journalArticle

Wojczynski, MK, Li, M, Bielak, LF, Kerr, KF, Reiner, AP, Wong, ND, Yanek, L, Qu, L, White, CC, Lange, LA, Ferguson, JF, He, J, Young, T, Mosley, TH, Smith, JA, Kral, BG, Guo, X, Wong, Q, Ganesh, SK, Heckbert, SR, Griswold, ME, O'Leary, DH, Budoff, M, Carr, JJ, Taylor, HA, Bluemke, DA, Demissie, S, Hwang, SJ, Paltoo, DN, Polak, JF, Psaty, BM, Becker, DM, Province, MA, Post, WS, O'Donnell, CJ, Wilson, JG, Harris, TB, Kavousi, M, Cupples, LA, Rotter, JI, Fornage, M, Becker, L, Peyser, PA, Borecki, IB & Reilly, MP 2013, 'Genetics of coronary artery calcification among African Americans, a meta-analysis', BMC Medical Genetics, vol. 14, no. 1, 75. https://doi.org/10.1186/1471-2350-14-75
Wojczynski MK, Li M, Bielak LF, Kerr KF, Reiner AP, Wong ND et al. Genetics of coronary artery calcification among African Americans, a meta-analysis. BMC Medical Genetics. 2013 Jul 19;14(1). 75. https://doi.org/10.1186/1471-2350-14-75
Wojczynski, Mary K. ; Li, Mingyao ; Bielak, Lawrence F. ; Kerr, Kathleen F. ; Reiner, Alex P. ; Wong, Nathan D. ; Yanek, Lisa ; Qu, Liming ; White, Charles C. ; Lange, Leslie A. ; Ferguson, Jane F. ; He, Jing ; Young, Taylor ; Mosley, Thomas H. ; Smith, Jennifer A. ; Kral, Brian G ; Guo, Xiuqing ; Wong, Quenna ; Ganesh, Santhi K. ; Heckbert, Susan R. ; Griswold, Michael E. ; O'Leary, Daniel H. ; Budoff, Matthew ; Carr, J. J. ; Taylor, Herman A. ; Bluemke, David A. ; Demissie, Serkalem ; Hwang, Shih Jen ; Paltoo, Dina N. ; Polak, Joseph F. ; Psaty, Bruce M. ; Becker, Diane M ; Province, Michael A. ; Post, Wendy S ; O'Donnell, Christopher J. ; Wilson, James G. ; Harris, Tamara B. ; Kavousi, Maryam ; Cupples, L. A. ; Rotter, Jerome I. ; Fornage, Myriam ; Becker, Lewis ; Peyser, Patricia A. ; Borecki, Ingrid B. ; Reilly, Muredach P. / Genetics of coronary artery calcification among African Americans, a meta-analysis. In: BMC Medical Genetics. 2013 ; Vol. 14, No. 1.
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TY - JOUR

T1 - Genetics of coronary artery calcification among African Americans, a meta-analysis

AU - Wojczynski, Mary K.

AU - Li, Mingyao

AU - Bielak, Lawrence F.

AU - Kerr, Kathleen F.

AU - Reiner, Alex P.

AU - Wong, Nathan D.

AU - Yanek, Lisa

AU - Qu, Liming

AU - White, Charles C.

AU - Lange, Leslie A.

AU - Ferguson, Jane F.

AU - He, Jing

AU - Young, Taylor

AU - Mosley, Thomas H.

AU - Smith, Jennifer A.

AU - Kral, Brian G

AU - Guo, Xiuqing

AU - Wong, Quenna

AU - Ganesh, Santhi K.

AU - Heckbert, Susan R.

AU - Griswold, Michael E.

AU - O'Leary, Daniel H.

AU - Budoff, Matthew

AU - Carr, J. J.

AU - Taylor, Herman A.

AU - Bluemke, David A.

AU - Demissie, Serkalem

AU - Hwang, Shih Jen

AU - Paltoo, Dina N.

AU - Polak, Joseph F.

AU - Psaty, Bruce M.

AU - Becker, Diane M

AU - Province, Michael A.

AU - Post, Wendy S

AU - O'Donnell, Christopher J.

AU - Wilson, James G.

AU - Harris, Tamara B.

AU - Kavousi, Maryam

AU - Cupples, L. A.

AU - Rotter, Jerome I.

AU - Fornage, Myriam

AU - Becker, Lewis

AU - Peyser, Patricia A.

AU - Borecki, Ingrid B.

AU - Reilly, Muredach P.

PY - 2013/7/19

Y1 - 2013/7/19

N2 - 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.

AB - 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.

KW - African-American

KW - Atherosclerosis

KW - Coronary artery calcium

KW - Genetics

KW - Meta-analysis

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