Abstract 15120: The Addition of a Genetic Risk Score to Traditional Risk Factors Improves Coronary Heart Disease Risk Prediction in the Atherosclerosis Risk in Communities (ARIC) Study
Aim: Recent studies have questioned the ability of genetic information to improve risk prediction for coronary heart disease (CHD) beyond traditional risk factors (TRF). We have designed a genetic risk score (GRS) based on single nucleotide polymorphisms (SNPs) selected from the literature according to predefined criteria. To evaluate the role of these genetic variants for CHD prediction, we examined whether addition of the GRS to TRF will improve CHD risk prediction
Methods: A prospective cohort of 8,542 white men and women from the Atherosclerosis Risk in Communities (ARIC) study was included in these analyses. SNPs in the GRS were selected from the literature based on an association with CHD, lack of association with a known intermediate CHD risk factor, and successful replication. Based on TRF alone, a Cox proportional hazards model was evaluated for the ARIC and Framingham risk scores. Assuming an additive model for each of the selected SNPs in the GRS, a Cox proportional hazards model was recalculated with addition of the GRS to traditional risk factors.
Results: There were 1,110 individuals (13%) that developed incident CHD during 18 years of follow-up. After meeting the predefined criteria, 14 SNPs were included in the GRS. Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification and calibration beyond that afforded by TRF alone. The area under the curve of the receiver operating characteristic increased from 0.742 to 0.749 (Δ= 0.007 95% CI: 0.005, 0.018). Calibration examined by the Grønnesby-Borgan goodness-of-fit metrics demonstrated a good fit (P>0.1). The net reclassification index (NRI) was 5.2%, and clinical NRI 15.1% demonstrating a substantial effect on the intermediate risk (5–20% 10-year CHD risk) categories where more than 20% of individuals were reclassified (Table).
Conclusion: A panel of SNPs can be helpful in improving risk classification especially for individuals who are at intermediate risk for CHD events. .
- © 2010 by American Heart Association, Inc.