Figure 1: Nature is not static. Left: Genetics drives variation in disease and pharmacogenetic response. The human body comprises hidden (or latent) linked networks of nodal sub-systems with edges representing physiome space (X). Centre: People have different genetically determined system dynamics (response Yt to a driving function of uncontrolled or controlled perturbations Z), that depend upon the system’s physiological state (y). Right: Dynamic response can be measured by phenotypes like: sti, slow relaxation time, delayed, etc. whether in the domain of disease progression or the development of e cacy or (lack of) safety. Genetic associations (i.e. the network nodes and their interrelations) discovered in an experiment will depend upon:-the choice of (sub)systems (design of X); the choice of phenotypes (design of Y); the partialing out of the confounding kinetics of (or exposure to) the Z drivers (z) (orthogonalisation and balance of X and Y with respect to Z); and, the (current) system state (i.e. the prevailing network edges) (a priori model for covariance structure constraints for X). *=convolve time varying functions.