Achieving consilience faces a number of potent challenges. In the human literature, we lack an organizing taxonomy of environmental exposures. Moreover, the lack of experimental control over environmental exposures, and in particular the tendency of multiple adverse exposures to cluster in the same individuals, families, neighborhoods etc., both cross-sectionally and over time, makes disentangling individual risk-factor effects that might interact with genetic differences a major challenge. While latent variable methods (e.g. inferring genetic effects from twin data) hold considerable promise for identifying major environmental domains that may moderate aggregate effects of genetic variants such methods, involving comparison of differences in familial correlation (e.g. in MZ-DZ correlation differences) as a function of environmental exposure, have relatively low power and thus can detect only large interaction effects (although it remains an open question whether they will yield greater insight into GXE effects than SNP by SNP GXE analyses, given the small effect sizes anticipated for the latter). Isolated reports of GXE effects in individual samples have in general not yet led to the coordinated efforts at cross-study replication, including meta-analyses, that would
