Schizophrenia Beyond Genome-Wide Association Studies: It's About Time

The discovery of potentially many hundreds of risk genes for schizophrenia does not resolve the mystery of the illness at the level of an individual. The diversity of implicated gene functions has encouraged speculation that there are convergent biological pathways that mediate risk at the systems level, perhaps represented in gene coexpression patterns. The authors emphasize that gene coexpression varies across development, with some molecular elements related to schizophrenia risk losing importance or gaining momentum over time. The systems biology of risk and environmental exposures associated with risk are both time-dependent. The authors propose that the dynamic gene-environment interplay subtended by shifting coexpression patterns may explain variable expressivity of genetic risk during development. In particular, gene-environment correlations provide a mechanism for the individual-hence for their genes-to affect the environment and thus individual experience, promoting chains of life events. The authors envision the paired study of molecular and behavioral patterns over time as a way to identify novel treatments and preventive strategies to change the course of schizophrenia.