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.
authors.affiliation: Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA. mwojczynski@wustl.edu
authors.forename: Mary K
authors.initials: MK
authors.lastname: Wojczynski
authors.forename: Mingyao
authors.initials: M
authors.lastname: Li
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Bielak
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Kerr
authors.forename: Alex P
authors.initials: AP
authors.lastname: Reiner
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Wong
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Yanek
authors.forename: Liming
authors.initials: L
authors.lastname: Qu
authors.forename: Charles C
authors.initials: CC
authors.lastname: White
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.forename: Jane F
authors.initials: JF
authors.lastname: Ferguson
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.forename: Taylor
authors.initials: T
authors.lastname: Young
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Smith
authors.forename: Brian G
authors.initials: BG
authors.lastname: Kral
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.forename: Quenna
authors.initials: Q
authors.lastname: Wong
authors.forename: Santhi K
authors.initials: SK
authors.lastname: Ganesh
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: Michael E
authors.initials: ME
authors.lastname: Griswold
authors.forename: Daniel H
authors.initials: DH
authors.lastname: O'Leary
authors.forename: Matthew
authors.initials: M
authors.lastname: Budoff
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.forename: Herman A
authors.initials: HA
authors.lastname: Taylor
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.forename: Serkalem
authors.initials: S
authors.lastname: Demissie
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Dina N
authors.initials: DN
authors.lastname: Paltoo
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Polak
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Diane M
authors.initials: DM
authors.lastname: Becker
authors.forename: Michael A
authors.initials: MA
authors.lastname: Province
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Post
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.forename: Maryam
authors.initials: M
authors.lastname: Kavousi
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Becker
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Peyser
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
mesh_terms: D001741:Black or African American / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D061205:Vascular Calcification / Q000235:genetics*
chemical_list: D008840:Microfilament Proteins; C570134:PHACTR1 protein, human