Prediction of coronary heart disease risk using a genetic risk score: the Atherosclerosis Risk in Communities Study.
Recent studies have evaluated whether incorporating nontraditional risk factors improves coronary heart disease (CHD) prediction models. This 1986-2001 US study aggregated the contribution of multiple single nucleotide polymorphisms into a genetic risk score (GRS) and assessed whether the GRS plus traditional risk factors predict CHD better than traditional risk factors alone. The Atherosclerosis Risk in Communities (ARIC) cohort was followed for a median of 13 years for CHD events (n = 1,452). Individuals were genotyped for 116 single nucleotide polymorphisms associated with CHD in multiple case-control studies. Single nucleotide polymorphisms nominally predicting incident CHD in the ARIC study were included in the GRS. The GRS was significantly associated with incident CHD in Blacks (hazard rate ratio = 1.20, 95% confidence interval: 1.11, 1.29) and Whites (hazard rate ratio = 1.10, 95% confidence interval: 1.06, 1.14) as well as in each tertile defined by the traditional cardiovascular risk score (p < or = 0.02). When receiver operating characteristic curves based on traditional risk factors were recalculated after the GRS was added, the increase in the area under the receiver operating characteristic curve was statistically significant for Blacks and suggestive of improved CHD prediction for Whites. This study demonstrates the concept of aggregating information from multiple single nucleotide polymorphisms into a risk score and indicates that it can improve prediction of incident CHD in the ARIC study.
Morrison
Alanna C
AC
Human Genetics Center and Division of Epidemiology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Bare
Lance A
LA
Chambless
Lloyd E
LE
Ellis
Stephen G
SG
Malloy
Mary
M
Kane
John P
JP
Pankow
James S
JS
Devlin
James J
JJ
Willerson
James T
JT
Boerwinkle
Eric
E
D050197:Atherosclerosis / Q000453:epidemiology*; D044383:Black People; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000209:etiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D044465:White People; D001741:Black or African American
D002784:Cholesterol