TY - JOUR
T1 - Integrative predictive model of coronary artery calcification in atherosclerosis
AU - McGeachie, Michael
AU - Badovinac Ramoni, Rachel L.
AU - Mychaleckyj, Josyf C.
AU - Furie, Karen L.
AU - Dreyfuss, Jonathan M.
AU - Liu, Yongmei
AU - Herrington, David
AU - Guo, Xiuqing
AU - Lima, João A.
AU - Post, Wendy
AU - Rotter, Jerome I.
AU - Rich, Stephen
AU - Sale, Michèle
AU - Ramoni, Marco F.
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Genetics
KW - Risk factors
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U2 - 10.1161/CIRCULATIONAHA.109.865501
DO - 10.1161/CIRCULATIONAHA.109.865501
M3 - Article
C2 - 19948975
AN - SCOPUS:73349101506
SN - 0009-7322
VL - 120
SP - 2448
EP - 2454
JO - Circulation
JF - Circulation
IS - 24
ER -