A multilocus genetic risk score predicts coronary heart disease risk in a Chinese Han population.

ABSTRACT

OBJECTIVE: Genome-wide association studies have identified multiple genetic loci associated with coronary heart disease (CHD) risk. However, whether these loci could improve the CHD risk prediction is unclear. METHODS AND RESULTS: The present case-control study (1146 CHD cases and 1146 controls) genotyped 19 recently discovered SNPs that associated with CHD risk. As a result, 10 SNPs were successfully replicated with odds ratios (ORs) ranging from 1.16 to 1.78 (P = 4.6 × 10(-2) to 5.99 × 10(-6)). A genetic risk score was constructed to assess the combined effects of the susceptibility loci on CHD risk. Subject in the second tertile (OR = 1.32, 95% CI, 1.02-1.73, P = 3.84 × 10(-2)) and the third tertile (OR = 2.62, 95% CI, 2.00-3.43, P = 3.18 × 10(-12)) had an increased risk of CHD comparing with those in the first genetic risk score tertile after adjustment for traditional risk factors including family history of CHD. Addition of the genetic risk score to the traditional model significantly improved the net reclassification as measured by the net reclassification index (NRI) (4.82%, P = 0.0001), however, no significant improvement was observed in discrimination of CHD, the area under the receiver operating characteristic curve (AUC) increased from 0.811 to 0.822 (P = 0.18). CONCLUSIONS: A multilocus genetic risk score was associated with CHD risk in a Chinese Han population. This genetic risk score improved the net reclassification but not improved the CHD discrimination. The potential clinical use of this variations remains to be defined.