Since studies have established an important role for smoking in DNA methylation [6–8], we hypothesized that tobacco smoking changes DNA methylation of genes in/near loci identified for CAD, which in turn could alter gene expression of these genes. We therefore investigated the association between DNA methylation of genes in/near CAD-GWAS loci in whole blood and tobacco smoking in the Rotterdam Study. Furthermore, we investigated the association between methylation and expression of CAD-related genes nearby the identified differentially methylated sites.