Genome-wide association studies have found single nucleotide polymorphisms (SNPs) at 13 genomic regions that are associated with coronary artery disease, myocardial infarction, or both. However, genetic discovery studies have the potential for several types of bias, therefore this prospective cohort study attempted to determine whether precise risk estimates could be made using these genetic association findings.

Overall, 1264 participants had a first coronary heart disease event during a median of 10.7 years’ follow-up. The authors constructed a multilocus genetic risk score for each individual by summoning the number of risk alleles (0/1/2) for each of the 13 SNPs associated with heart disease, weighted according to their estimated effect sizes. When compared with the bottom quintile of the genetic risk score, those in the top quintile were at 1.66-times increased risk of coronary heart disease after adjusting for traditional risk factors. The genetic risk score did not have a significant effect on net reclassification improvement (p=0.18), however it did have a small effect on integrated discrimination index (p=0.0006).

Conclusions

In this prospective cohort study, a genetic risk score based on 13 SNPs associated with coronary artery disease identified 20% of individuals who were at a roughly 70% increased risk of a first coronary heart disease event.

▶ Ripatti S, Tikkanen E, Orho-Melander M, et al. A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses. Lancet 2010;376:1393–400.