Genetic predisposition to coronary heart disease and stroke using an additive genetic risk score: A population-based study in Greece

ObjectiveTo determine the extent to which the risk for incident coronary heart disease (CHD) increases in relation to a genetic risk score (GRS) that additively integrates the influence of high-risk alleles in nine documented single nucleotide polymorphisms (SNPs) for CHD, and to examine whether this GRS also predicts incident stroke.MethodsGenotypes at nine CHD-relevant SNPs were determined in 494 cases of incident CHD, 320 cases of incident stroke and 1345 unaffected controls drawn from the population-based Greek component of the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. An additive GRS was calculated for each study participant by adding one unit for the presence of each high-risk allele multiplied by the estimated effect size of that allele in the discovery samples. Statistical analysis was performed using logistic regression.ResultsThe GRS was significantly associated with the incidence of CHD where the odds of CHD incidence in the highest quintile of the GRS were 1.74 times higher (95% confidence interval [CI] = 1.25-2.43, p for trend = 0.0004), compared to the lowest quintile. With respect to stroke, a weaker and non-significant positive association with GRS was apparent as the odds of stroke incidence in the highest quintile of the GRS were 1.36 times higher (95% CI = 0.90-2.06, p for trend = 0.188), compared to the lowest quintile.ConclusionA GRS relying on nine documented “CHD-specific” SNPs is significantly predictive of CHD but it was not found to be statistically significantly associated with incident stroke.

► We constructed a genetic risk score based on 9 “CHD-specific” SNPs from GWAS. ► We examined whether this genetic risk score (GRS) predicts incident CHD and stroke. ► We have used resources generated in the Greek-EPIC cohort. ► The GRS was significantly associated with the incidence of CHD. ► This GRS was not found to be statistically significantly associated with incident stroke.