Assessment of the value of a genetic risk score in improving the estimation of coronary risk
Lluis–Ganella C et al. – A multi–locus genetic risk score (GRS) based on genetic variants unrelated to cardiovascular risk factors (CVRFs) was associated with a linear increase in risk of coronary heart disease (CHD) events in two distinct populations. This GRS improves risk reclassification particularly in the population at intermediate coronary risk. These results indicate the potential value of the inclusion of genetic information in classical functions for risk assessment in the intermediate risk population group.Methods
- Using eight genetic variants associated with CHD but not with classical cardiovascular risk factors (CVRFs), the authors generated a multi–locus GRS, and found it to be linearly associated with CHD in two population based cohorts: The REGICOR Study (n=2351) and The Framingham Heart Study (n=3537) (meta–analyzed HR [95%CI]: ~1.13 [1.01–1.27], per unit).
- Inclusion of the GRS in the Framingham risk function improved its discriminative capacity in the Framingham sample (c–statistic: 72.81 vs.72.37, p=0.042) but not in the REGICOR sample.
- According to both the net reclassification improvement (NRI) index and the integrated discrimination index (IDI), the GRS improved re–classification among individuals with intermediate coronary risk (meta–analysis NRI [95%CI]: 17.44 [8.04; 26.83]), but not overall.