Open Access BASE2013

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

Wojczynski, M.K. (Mary ); Li, M. (Mingyao); Bielak, L.F. (Lawrence F.); Kerr, K.F. (Kathleen); Reiner, A. (Alexander); Wong, N.D. (Nathan); Yanek, L.R. (Lisa); Qu, L. (Liming); White, C.C. (Charles); Lange, L.A. (Leslie); Ferguson, J.F. (Jane); He, J. (Jing); Young, T. (Taylor); Mosley, T.H. (Thomas); Smith, J.A. (Jennifer A); Kral, B.G. (Brian); Guo, X. (Xiuqing); Wong, Q. (Quenna); Ganesh, S.K. (Santhi); Heckbert, S.R. (Susan); Griswold, M.D. (Michael); O'Leary, D.H. (Daniel H.); Budoff, M.J. (Matthew); Carr, J. (Jeffrey); Taylor, H.A. (Herman); Bluemke, D.A. (David); Demissie, S. (Serkalem); Hwang, S.-J. (Shih-Jen); Paltoo, D.N. (Dina); Polak, J.F. (Joseph F.); Psaty, B.M. (Bruce); Becker, D.M. (Diane); Province, M.A. (Mike); Post, W.S. (Wendy S.); O'Donnell, C.J. (Christopher); Wilson, J.G. (James); Harris, T.B. (Tamara); Kavousi, M. (Maryam); Cupples, L.A. (Adrienne); Rotter, J.I. (Jerome); Fornage, M. (Myriam); Becker, L.C. (Lewis); Peyser, P.A. (Patricia A.); Borecki, I.B. (Ingrid); Reilly, M.P. (Muredach)

Open Access

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 n

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