Genetic predisposition for cardiovascular disease (CVD) is likely to be modified by environmental exposures. We tested if the associated risk of CVD and CVD-mortality by the single nucleotide polymorphism rs4977574 on chromosome 9p21 is modified by life-style factors.
A total of 24,944 middle-aged subjects (62% females) from the population-based Malm?-Diet-and-Cancer-Cohort were genotyped. Smoking, education and physical activity-levels were recorded. Subjects were followed for 15 years for incidence of coronary artery disease (CAD; N?=?2309), ischemic stroke (N?=?1253) and CVD-mortality (N?=?1156). Multiplicative interactions between rs4977574 and life-style factors on endpoints were tested in Cox-regression-models. We observed an interaction between rs4977574 and smoking on incident CAD (P?=?0.035) and CVD-mortality (P?=?0.012). The hazard ratios (HR) per risk allele of rs4977574 were highest in never smokers (N?=?9642) for CAD (HR?=?1.26; 95% CI 1.13-1.40; P