Functional analysis of genetic variants in association with human complex diseases remains a challenge for modern research. Discovery of gene–gene interactions may represent an additional tool for identifying specific polymorphisms involved in disease development. It not only identifies new candidate genes for mechanistic studies, but also suggests biological relations in the function of these genes with certain variants in developing disease. We describe a few examples of the studies where a link between statistical evidence of gene–gene interaction was found with the expression or function of genes of interest. Finally, we present future perspectives for integration genetic epidemiology data with biologically relevant mechanisms of disease.