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

Authors: YIANNAKOURIS, NIKOLAOS - Harokopio University Of Athens; KATSOULIS, M. - Hellenic Health Foundation; DILIS, VARDIS - Hellenic Health Foundation; Parnell, Laurence; TRICHOPOULOS, DIMITRIOS - Harvard School Of Public Health; ORDOVAS, JOSE M. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; TRICHOPOULOU, ANTONIA - University Of Athens

Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/20/2012
Publication Date: 2/28/2012
Citation: Yiannakouris, N., Katsoulis, M., Dilis, V., Parnell, L.D., Trichopoulos, D., Ordovas, J., Trichopoulou, A. 2012. Genetic predisposition to coronary heart disease and stroke using an additive genetic risk score: a population-based study in Greece. Atherosclerosis. 222(1):175-179.

Interpretive Summary: In the last several years many individual genetic factors have been found to be associated with the risk of coronary heart disease (CHD), but it is not known to what extent the factors conferring this increased risk can be added together to form a composite genetic risk score (GRS). Thus, the objectives of this study were to integrate the impact of nine high-risk genetic variants for CHD in a combined analysis and to assess the relationship between this GRS and stroke. This was undertaken in the Greek component of the European Prospective Investigation into Cancer and Nutrition study. The GRS was determined for each individual in the study by assigning one unit for the presence of each high-risk genetic variant, and weighting each based on the estimated impact of that single variant. Our results showed that the GRS was significantly associated with CHD occurrence where the individuals with a GRS in the highest quintile (top 20% of all scores). They were 1.74 times more likely to have CHD compared to those persons within the lowest 20% of GRS scores. When comparing these same highest and lowest 20% GRS groups for risk of stroke, there was a 1.36 times greater chance for those in the topmost GRS group to develop stroke, but this was not statistically significant. In conclusion, it is clear that a combined genetic risk score based on nine common CHD variants is significantly predictive of CHD, but is not useful in determining genetic basis for stroke risk.

Technical Abstract: Objective: To 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. Methods: Genotypes 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. Results: The 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. Conclusion: A 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.