Biometric and developmental gene-environment interactions: looking back, moving forward.

A history of research on gene-environment interaction (G x E) is provided in this article, revealing the fact that there have actually been two distinct concepts of G x E since the very origins of this research. R. A. Fisher introduced what I call the biometric concept of G x E (G x EB), whereas Lancelot Hogben introduced what I call the developmental concept of G x E (G x ED). Much of the subsequent history of research on G x E has largely consisted of the separate legacies of these separate concepts, along with the (sometimes acrimonious) disputes that have arisen time and again when employers of each have argued over the appropriate way to conceptualize the phenomenon. With this history in place, more recent attempts to distinguish between different concepts of G x E are considered, paying particular attention to the commonly made distinction between "statistical interaction" and "interactionism," and Michael Rutter's distinction between statistical interaction and "the biological concept of interaction." I argue that the history of the separate legacies of G x EB and G x ED better supports Rutter's analysis of the situation and that this analysis best paves the way for an integrative relationship between the various scientists investigating the place of G x E in the etiology of complex traits.