Our results support that a more complete picture of factors influencing DNA methylation should include genotype information and could also help to detect environmental influences that may only be unmasked in the context of a specific genetic background. This highlights the importance of including both individual genetic differences as well as environmental phenotypes into epigenetic studies and also the importance of improving our ability to identify environmental associations. Our data also support the disease relevance of variants predicting DNA methylation together with the environment beyond main meQTL effects, and the view that there are functional differences of additive and interactive effects of genes and environment on DNA methylation. Improved understanding of these functional differences may also yield novel insights into pathophysiological mechanisms of common non-communicable diseases, as risk for all of these disorders is driven by both genetic and environmental factors.