title: Associations between a Genetic Risk Score for Clinical CAD and Early Stage Lesions in the Coronary Artery and the Aorta.
abstract: OBJECTIVE
  The correlation between the extent of fatty streaks, more advanced atherosclerotic lesions, and community rates of coronary artery disease (CAD) is substantially higher for the coronary artery compared to the aorta. We sought to determine whether a genetic basis contributes to these differences.
  
  
  RESULTS
  We conducted a cluster analysis of 6 subclinical atherosclerosis phenotypes documented in 564 white participants of the Pathobiological Determinants of Atherosclerosis in Youth study including the extent of fatty streaks and raised lesions in the coronary artery (CF and CR), thoracic aorta (TF and TR), and abdominal aorta (AF and AR) followed by a genetic association analysis of the same phenotypes. Our cluster analysis grouped all raised lesions and fatty streaks in the coronary into one cluster (CF, CR, TR, and AR) and the fatty streaks in the aorta into a second cluster (TF and AF). We found a genetic risk score of high-risk alleles at 57 susceptibility loci for CAD to be variably associated with the phenotypes in the first cluster (OR: 1.30 p = 0.009 for being in top quartile of degree of involvement of CF, 1.34 p = 0.005 for CR, 1.25: p = 0.11 for TR, and 1.19 p = 0.08 for AR) but not at all with the phenotypes in the second cluster (OR: 1.01, p = 0.95 for TF and 0.98, p = 0.82 for AF).
  
  
  CONCLUSIONS
  The genetic determinants of fatty streaks in the aorta do not appear to overlap substantially with the genetic determinants of fatty streaks in the coronary as well as raised lesions in both the coronary and the aorta. These findings may explain why a larger fraction of fatty streaks in the aorta are less likely to progress to raised lesions compared to the coronary artery.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America.|Stanford Cardiovascular Institute, Stanford University, Stanford, California, United States of America.
authors.forename: Elias L
authors.identifier: http://orcid.org/0000-0002-2938-6424
authors.initials: EL
authors.lastname: Salfati
authors.affiliation: Wake Forest University Baptist Medical Center, Medical Center Boulevard, Winston-Salem, North Carolina 27157, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Herrington
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America.|Stanford Cardiovascular Institute, Stanford University, Stanford, California, United States of America.
authors.forename: Themistocles L
authors.identifier: http://orcid.org/0000-0003-2349-0009
authors.initials: TL
authors.lastname: Assimes
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001011:Aorta / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D016000:Cluster Analysis; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology*; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D055815:Young Adult