Deconvoluting gene and environment interactions to develop an “epigenetic score meter” of disease

Human health is determined both by genetics (G) and environment (E). This is clearly illustrated in groups of individuals who are exposed to the same environmental factor showing differential responses. A quantitative measure of the gene-environment interactions (GxE) effects has not been developed and in some instances, a clear consensus on the concept has not even been reached; for example, whether cancer is predominantly emerging from “bad luck” or “bad lifestyle” is still debated. In this article, we provide a panel of examples of GxE interaction as drivers of pathogenesis. We highlight how epigenetic regulations can represent a common connecting aspect of the molecular bases. Our argument converges on the concept that the GxE is recorded in the cellular epigenome, which might represent the key to deconvolute these multidimensional intricated layers of regulation. Developing a key to decode this epigenetic information would provide quantitative measures of disease risk. Analogously to the epigenetic clock introduced to estimate biological age, we provocatively propose the theoretical concept of an “epigenetic score-meter” to estimate disease risk.