Cigarette smoking is a major risk factor for atherosclerosis [52]. In GHS participants, the prevalence of atherosclerotic plaques in the right and left carotid arteries, assessed by echography, was strongly increased in smokers (P = 9.1×10−7 after adjustment for age and gender). Among the 18 gene expressions independently associated with smoking, four were individually correlated with the number of carotid plaques, PTGDS (P = 1.8×10−7) negatively and MMP25 (P = 3.5×10−4), SASH1 (P = 1.4×10−5) and WWC3 (P = 6.3×10−4) positively ( Table 7 ). In a multivariate model including the four expression traits and smoking, as well as age and gender, PTGDS (P = 5.7×10−4) and SASH1 (P = 0.012) remained significantly associated with the number of plaques whereas MMP25 (P = 0.09), WWC3 (P = 0.10) and smoking (P = 0.5) were no longer significant, suggesting that the association between smoking and atherosclerosis was mostly reflected (or mediated) by its effect on the expression of these four genes. The fact that PTGDS and SASH1 expression remained associated with carotid plaques after adjustment on smoking status may indicate a
