The polygenicity of psychiatric disorders poses intriguing difficulties: how can these many genes be coherently tied together? A parsimonious hypothesis is that the polygenic basis of a psychiatric disorder is manifest in the regulation or function of one or more known or novel pathways. Genetic variation at many different loci could introduce numerous slight alterations that result in a pathway that is insufficiently robust in response to an environmental insult or that leads to an inappropriate developmental program. 137 Risk for a complex psychiatric disorder could be conferred by the emergent properties of the pathway itself rather than any single component. For SCZ, this conceptualization is supported by the risk profile findings for SCZ, and by the miR-137 results that hint at an underlying regulatory network. For ASD, typical patterns of cortical gene expression in frontal and temporal cortex have been found to be attenuated in ASD cases compared to controls, and an empirically-derived gene expression module that is under-expressed in ASD was found to be enriched for known ASD susceptibility genes and genetic association signals. 90
