Integrative predictive model of coronary artery calcification in atherosclerosis.
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).


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.
McGeachie
Michael
M
Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Ramoni
Rachel L Badovinac
RL
Mychaleckyj
Josyf C
JC
Furie
Karen L
KL
Dreyfuss
Jonathan M
JM
Liu
Yongmei
Y
Herrington
David
D
Guo
Xiuqing
X
Lima
João A
JA
Post
Wendy
W
Rotter
Jerome I
JI
Rich
Stephen
S
Sale
Michèle
M
Ramoni
Marco F
MF
D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000208:ethnology / Q000235:genetics*; D001499:Bayes Theorem; D002114:Calcinosis / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D011237:Predictive Value of Tests; D012307:Risk Factors; D044465:White People / Q000208:ethnology / Q000235:genetics