Integrative predictive model of coronary artery calcification in atherosclerosis

Michael McGeachie, Rachel L. Badovinac Ramoni, Josyf C. Mychaleckyj, Karen L. Furie, Jonathan M. Dreyfuss, Yongmei Liu, David Herrington, Xiuqing Guo, João A. Lima, Wendy Post, Jerome I. Rotter, Stephen Rich, Michèle Sale, Marco F. Ramoni

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background-: Many different genetic and clinical factors have been identified as causes or contributors to atherosclerosis. We present a model of preclinical atherosclerosis based on genetic and clinical data that predicts the presence of coronary artery calcification in healthy Americans of European descent 45 to 84 years of age in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods and Results-: We assessed 712 individuals for the presence or absence of coronary artery calcification and assessed their genotypes for 2882 single-nucleotide polymorphisms. With the use of these single-nucleotide polymorphisms and relevant clinical data, a Bayesian network that predicts the presence of coronary calcification was constructed. The model contained 13 single-nucleotide polymorphisms (from genes AGTR1, ALOX15, INSR, PRKAB1, IL1R2, ESR2, KCNK1, FBLN5, PPARA, VEGFA, PON1, TDRD6, PLA2G7, and 1 ancestry informative marker) and 5 clinical variables (sex, age, weight, smoking, and diabetes mellitus) and achieved 85% predictive accuracy, as measured by area under the receiver operating characteristic curve. This is a significant (P<0.001) improvement on models that use just the single-nucleotide polymorphism data or just the clinical variables. Conclusions-: We present an investigation of joint genetic and clinical factors associated with atherosclerosis that shows predictive results for both cases, as well as enhanced performance for their combination.

Original languageEnglish (US)
Pages (from-to)2448-2454
Number of pages7
JournalCirculation
Volume120
Issue number24
DOIs
StatePublished - Dec 2009

Keywords

  • Atherosclerosis
  • Genetics
  • Risk factors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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