Studying the Exposome to Understand the Environmental Determinants of Complex Liver Diseases

: The development of complex disease (i.e., non-Mendelian disease) has long been postulated to be driven by environmental pressures in genetically susceptible individuals. To date, however, research has largely been focused on delineating the genetic drivers of disease, with limited attention devoted to the contribution of external exposures. The exposome, defined as the cumulative effect of environmental exposures and the associated biological response across the lifespan, is now recognized as a key measure for precision medicine. In this review, we discuss the concept, principles, approaches, and current status of exposome research as well as existing knowledge regarding environmental determinants of selected liver diseases. Conclusion: There is abundant preliminary evidence that environmental exposures modify the risk of liver disease. Untargeted exposome research promises to launch a new era in the study of liver disease, enabling the use of precision medicine approaches that can inform new public health initiatives, biomarker discovery, and novel therapies.