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


METHODS
A case-control study.


METHODS
The general Greek population of the EPIC study.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Genetic predisposition to CHD, operationalised through a multilocus GRS, and ConvRFs have essentially additive effects on CHD risk.
Hellenic Health Foundation, Athens, Greece.
Nikos
N
Yiannakouris
Michail
M
Katsoulis
Antonia
A
Trichopoulou
Jose M
JM
Ordovas
Dimitrios
D
Trichopoulos
D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D003327:Coronary Disease / Q000453:epidemiology* / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D038441:Diet, Mediterranean; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006115:Greece / Q000453:epidemiology; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
Epidemiology; Genetics