title: Common genetic variants and subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).
abstract: OBJECTIVE
  Subclinical atherosclerosis (sCVD), measured by coronary artery calcium (CAC) and carotid intima media thickness (CIMT) is associated with cardiovascular disease (CVD). Genome-Wide Association Studies (GWAS) of sCVD and CVD have focused primarily on Caucasian populations. We hypothesized that these associations may differ in populations from distinct genetic backgrounds.
  
  
  METHODS
  The associations between sCVD and 66 single nucleotide polymorphisms (SNPs) from published GWAS of sCVD and CVD were tested in 8224 Multi-Ethnic Study of Atherosclerosis (MESA) and MESA Family participants [2329 Caucasians (EUA), 691 Chinese (CHN), 2482 African Americans (AFA), and 2012 Hispanic (HIS)] using an additive model adjusting for CVD risk factors, with SNP significance defined by a Bonferroni-corrected p < 7.6 × 10(-4) (0.05/66).
  
  
  RESULTS
  In EUA there were significant associations for CAC with SNPs in 9p21 (rs1333049, P = 2 × 10(-9); rs4977574, P = 4 × 10(-9)), COL4A1 (rs9515203, P = 9 × 10(-6)), and PHACTR1 (rs9349379, P = 4 × 10(-4)). In HIS, CAC was associated with SNPs in 9p21 (rs1333049, P = 8 × 10(-5); rs4977574, P = 5 × 10(-5)), APOA5 (rs964184, P = 2 × 10(-4)), and ADAMTS7 (rs7173743, P = 4 × 10(-4)). There were no associations between CAC and 9p21 SNPs for AFA and CHN. Fine mapping of the 9p21 region revealed SNPs with robust associations with CAC in EUA and HIS but no significant associations in AFA and CHN.
  
  
  CONCLUSIONS
  Our results suggest some shared genetic architecture for sCVD across ethnic groups, while also underscoring the possibility of novel variants and/or pathways in risk of CVD in ethnically diverse populations.
authors.affiliation: MedStar Health Research Institute, Georgetown University Hospital, Washington, DC, USA; National Institutes of Health, Radiology and Imaging Sciences, Bethesda, MD, USA.
authors.forename: Jose D
authors.initials: JD
authors.lastname: Vargas
authors.affiliation: Center for Public Health and Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA; Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
authors.forename: Ani
authors.initials: A
authors.lastname: Manichaikul
authors.affiliation: Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
authors.forename: Xin-Qun
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Center for Public Health and Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Institute for Translational Genomics and Population Sciences, Torrance, CA, USA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Post
authors.affiliation: Department of Radiology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Polak
authors.affiliation: Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.affiliation: National Institutes of Health, Radiology and Imaging Sciences, Bethesda, MD, USA. Electronic address: bluemked@cc.nih.gov.
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000208:ethnology / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D020641:Polymorphism, Single Nucleotide; D014481:United States / Q000453:epidemiology
chemical_list: D005819:Genetic Markers
keywords: Coronary calcium; Genetics; Intima-medial thickness; Single nucleotide polymorphism