Epigenetics and the Exposome: environmental exposure in disease etiology

While genomics has been founded on accurate tools that lead to a limited amount of classification error, exposure assessment in epidemiology is often affected by large error. The “environment” is in fact a complex construct that encompasses chemical exposures (e.g., to carcinogens); biological agents (viruses, or the “microbiome”); and social relationships. The “exposome” concept was then put forward to stress the relatively poor development of appropriate tools for exposure assessment when applied to the study of disease etiology. Three layers of the exposome have been proposed: “general external” (including social capital, stress and psychology); “specific external” (including chemicals, viruses, radiation, etc.); and “internal” (including for example metabolism and gut microflora). In addition, there are at least three properties of the exposome: (a) it is based on a refinement of tools to measure exposures (including internal measurements in the body); (b) it involves a broad definition of “exposure” or environment, including overarching concepts at a societal level; and (c) it involves a temporal component (i.e., exposure is analyzed in a life-course perspective). The conceptual and practical challenge is how the different layers (i.e., general, specific external, and internal) connect to each other in a causally meaningful sequence. The relevance of this question pertains to the translation of science into policy—for example, if experiences in early life impact on the adult risk of disease, and on the quality of aging, how is distant action to be incorporated in biological causal models and into policy interventions? A useful causal theory to address scientific and policy question about exposure is based on the concept of information transmission. Such a theory can explain how to connect the different layers of the exposome in a life-course temporal frame and helps identify the best level for intervention (molecular, individual, or population level). In this context epigenetics plays a key role, partly because it explains the long-distance persistence of epigenetic changes via the concept of “epigenetic memory.”