Abstract 19965: Reclassification of 10-y Coronary Heart Disease Risk Probability by Incorporating Genetic Markers; Insights from the Mayo electronic MEdical Records and GEnomics (eMERGE) Study.
Background: Susceptibility variants identified by genome-wide association studies (GWAS) have modest odds ratios (ORs). Whether such variants provide incremental risk prediction beyond the Framingham Risk Score (FRS) is unclear.
Methods: In the Mayo electronic MEdical Records and GEnomics (eMERGE) cohort, ascertained for a GWAS of peripheral arterial disease, 1,262 controls without cardiovascular disease were identified. The 10-y probability of CHD for each individual was calculated based on age, sex, total and HDL cholesterol, blood pressure, diabetes, and smoking status (Wilson et al., Circulation, 1998). We selected 11 replicated SNPs identified in GWAS to be associated with CHD. Four of these were genotyped on the Human660Quad_v1 GWAS platform, and genotypes for 7 SNPs were imputed from HapMap CEU population using MACH. We calculated a modified FRS by incorporating genetic information into the baseline FRS for each patient, based on number of risk alleles and the ORs associated with each risk allele. The net reclassification rate was calculated by comparing proportion of patients who would be reclassified into higher- or lower-risk groups.
Results: Reclassification of the 10-y CHD probability with the addition of genotypes of 11 SNPs is summarized in the Table. After inclusion of genotype information, a total of 386 individuals (30.6%) were reclassified into higher- (190) or lower- risk groups (196), which led to a net reclassification rate of -0.5% [(190-196)/1262]. The number of individuals in intermediate and intermediate-high risk groups decreased by 36 and 9, respectively, whereas 28 and 15 additional individuals were classified as low- or high-risk.
Conclusion: Adding genotypes at 11 susceptibility SNPs to the FRS in 1,262 adults led to significant reclassification in the 10-y CHD risk. Genetic information may have clinical utility in refining CHD risk stratification.
- © 2010 by American Heart Association, Inc.