Gene-Environment Interaction in the Era of Precision Medicine -- Fix the Potholes or Start Building a New Road?

Abstract: Genetic mapping sprung in the last decade of the 20th century with the development of statistical procedures putting classical models of genetic effects together with molecular biology techniques. It eventually became clear that those models, originally developed to serve other purposes, implied limitations at different stages of the analyses-disclosing loci, measuring their effects and providing additional parameters for adequate biological/medical interpretations. The present paper is aimed to ponder whether it is realistic and worth to try and further amend classical models of genetic effects or it proves more sensible to undertake alternative theoretical strategies instead. In order to further feed into that debate, mathematical developments for gene-environment interaction stemming from the classical models of genetic effects are here revised and brought up-to-date with the prospects present-day available data bestow, particularly in the context of precision medicine. Those developments strengthen the methodology required to overcome the COVID-19 pandemic.