Heart Care Info - Heart Disease Prevention & Treatment

A Genetic Risk Score is Associated with Incident Cardiovascular Disease and Coronary Artery Calcium-The Framingham Heart Study

G Thanassoulis, GM Peloso, MJ Pencina... - Circulation: ..., 2012 - Am Heart Assoc... The addition of recently discovered SNPs did not significantly improve the performance of this GRS. Key words: Genetics, single nucleotide polymorphisms, cardiovascular disease, coronary heart disease, risk prediction, reclassification ...

Methods and Results—Using findings from recent GWAS, we constructed genetic risk scores (GRS) comprised of 13 genetic variants associated with myocardial infarction (MI) or other manifestations of CHD and 102 genetic variants associated with CHD or its major risk factors. We also updated the 13 SNP GRS with 16 SN Ps recently discovered by GWAS. We estimated the association, discrimination and risk reclassification of each GRS for incident cardiovascular events and for prevalent coronary artery calcium (CAC). In analyses adjusted for age, sex, CVD risk factors and parental history of CVD, the 13 SNP GRS was significantly associated with incident hard CHD (HR 1.07, 95% CI 1.00-1.15, p=0.04), CVD (hazard ratio [HR] per-allele 1.05, 95% confidence interval [CI] 1.01-1.09; p=0.03), and high CAC (defined as >75th age and sex-specific percentile; odds ratio [OR] per-allele 1.18, 95% CI 1.11-1.26, p=3.4 x 10-7). The GRS did not improve discrimination for incident CHD or CVD but led to modest improvements in risk reclassification. However, significant improvements in discrimination and risk reclassification were observed for the prediction of high CAC. The addition of 16 newly discovered SN Ps to the 13 SNP GRS did not significantly modify these results.

Conclusions—A GRS comprised of 13 SN Ps associated with coronary disease is an independent predictor of cardiovascular events and of high CAC, modestly improves risk reclassification for incident CHD and significant improves discrimination for high CAC. The addition of recently discovered SN Ps did not significantly improve the performance of this GRS.