Gene-Environment Interaction in the Era of Precision Medicine - Filling the Potholes Rather Than Starting to Build a New Road.

Gene-environment interaction is a key part of evolutionary biology, animal, and plant breeding, and a number of health sciences, like epidemiology and precision medicine. However, bottlenecks in models of gene-environment interaction have recently been made manifest, particularly in the field of medicine and, consequently, specific improvements have been explicitly requested-namely, an implementation of gene-environment interaction satisfactorily disentangled from gene-environment correlation. The present paper meets those demands by providing mathematical developments that implement classical models of genetic effects and bring them up to date with the prospects current available data bestow. These developments are shown to overcome the limitations of previous proposals through the analysis of illustrative examples on disease susceptibility, with special attention paid to precision medicine. Indeed, a number of misconceptions about the application of models of genetic/environmental effects to precision medicine are here identified and clarified. The theory here provided is argued to strengthen, in particular, the methodology required for high-precision characterization of strain virulence in the study of the COVID-19 pandemic.