John Jeffrey Carr
Professor of Radiology, Biomedical Informatics and Cardiovascular Medicine
Last active: 9/11/2017

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

Wojczynski MK, Li M, Bielak LF, Kerr KF, Reiner AP, Wong ND, Yanek LR, 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 LC, Peyser PA, Borecki IB, Reilly MP
BMC Med Genet. 2013 14: 75

PMID: 23870195 · PMCID: PMC3733595 · DOI:10.1186/1471-2350-14-75

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.

MeSH Terms (9)

African Americans Atherosclerosis Coronary Artery Disease Genome-Wide Association Study Genotype Humans Microfilament Proteins Polymorphism, Single Nucleotide Vascular Calcification

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