A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses.

Description

The aim of this study was to validate recently discovered genetic risk factors for coronary heart disease and to estimate the magnitude of risk conferred by these genetic risk factors in the population setting. For that purpose, the authors investigated 13 recently discovered single nucleotide polymorphisms (SNPs) associated with coronary heart disease in a case-control design including 3,829 participants with prevalent coronary heart disease and 48,897 controls; as well as in a prospective cohort design including 30,725 participants free of cardiovascular disease. In the prospective cohort analyses, 1,264 incident cases of first coronary heart disease were recorded during a median follow-up of 10.7 years. By developing a genetic risk score based on the 13 SNPs identified from genome-wide association studies for coronary heart disease, the authors found that an elevated genetic risk score was associated with a 1.7 times increased risk of having a first coronary heart disease event than those with a lower genetic risk score. Although strongly associated with risk of incident coronary heart disease, genetic risk score did not improve risk discrimination over traditional risk factors when assessed by the C index. However, when assessed by newer approaches to estimate risk discrimination such as IDI (integrated discrimination improvement) and clinical NRI (net reclassification improvemement), the genetic risk score slightly improved risk prediction for coronary heart disease. These findings suggest that the identification of these specific genetic regions associated with coronary heart disease can be used in the general population, but the clinical use of this grouping of SNPs requires further studies. In their comment, Sandhu M et al. discussed the fact that the use of genomic risk prediction alone for common disease with relatively small familial relative risks will probably never be possible to predict individual disease risk, but its use in conjunction with conventional risk factors warrant more studies.