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Title: Additive influence of genetic predisposition and conventional risk factors in the incidence of coronary heart disease: a population-based study in Greece

Author
item YIANNAKOURIS, NIKOS - Harokopio University Of Athens
item KATSOULIS, MICHAIL - Hellenic Health Foundation
item TRICHOPOULOU, ANTONIA - Hellenic Health Foundation
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item TRICHOPOULOS, DIMITRIOS - Hellenic Health Foundation

Submitted to: BMJ Open
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/10/2013
Publication Date: 2/5/2014
Citation: Yiannakouris, N., Katsoulis, M., Trichopoulou, A., Ordovas, J.M., Trichopoulos, D. 2014. Additive influence of genetic predisposition and conventional risk factors in the incidence of coronary heart disease: a population-based study in Greece. BMJ Open. DOI: 10.1136/bmjopen-2013-004387.

Interpretive Summary: Coronary heart disease (CHD) results from complex interactions between genetic and environmental factors, with dietary habits being most influential. In previous studies we developed a combination of gene variants that was predictive of CHD that we named CHD genetic risk score (GRS). In the present study we have investigated the interactions of the CHD-GRS with several traditional cardiovascular risk factors, including smoking, hypertension, type-2 diabetes mellitus (T2DM), body mass index (BMI), physical activity and adherence to the Mediterranean diet, which has been shown to protect against CHD. For this purpose we have used a case-control study including 477 patients with medically confirmed incident CHD and 1271 controls. Our results show that the joint presence of a high GRS and high load of traditional CHD risk factors was in all instances associated with an increased risk of CHD, compared with the joint presence of a low GRS and low load of traditional CHD risk factors. Moreover, our data revealed that the effects of the genetic and non-genetic risk factors was additive and had similar weights. Therefore, these data supports the importance of controlling traditional risk factors using behavioral modification (i.e., Mediterranean diet) in order to curtail the current CHD epidemic.

Technical Abstract: An additive genetic risk score (GRS) for coronary heart disease (CHD) has previously been associated with incident CHD in the population-based Greek European Prospective Investigation into Cancer and nutrition (EPIC) cohort. In this study, we explore GRS-‘environment’ joint actions on CHD for several conventional cardiovascular risk factors (ConvRFs), including smoking, hypertension, type-2 diabetes mellitus (T2DM), body mass index (BMI), physical activity and adherence to the Mediterranean diet. This was a case–control study in the general Greek population of the EPIC study. 477 patients with medically confirmed incident CHD and 1271 controls participated in this study. We estimated the ORs for CHD by dividing participants at higher or lower GRS and, alternatively, at higher or lower ConvRF, and calculated the relative excess risk due to interaction (RERI) as a measure of deviation from additivity. The joint presence of higher GRS and higher risk ConvRF was in all instances associated with an increased risk of CHD, compared with the joint presence of lower GRS and lower risk ConvRF. The OR (95% CI) was 1.7 (1.2 to 2.4) for smoking, 2.7 (1.9 to 3.8) for hypertension, 4.1 (2.8 to 6.1) for T2DM, 1.9 (1.4 to 2.5) for lower physical activity, 2.0 (1.3 to 3.2) for high BMI and 1.5 (1.1 to 2.1) for poor adherence to the Mediterranean diet. In all instances, RERI values were fairly small and not statistically significant, suggesting that the GRS and the ConvRFs do not have effects beyond additivity. Genetic predisposition to CHD, operationalized through a multilocus GRS, and ConvRFs have essentially additive effects on CHD risk.