The highly polygenic nature of psychiatric disease and the failure of genome-wide studies to support the role of candidate genes (with a few exceptions) suggest that generalizable mechanistic insight is unlikely to be obtained from analysis of a single dysfunctional molecule in isolation. Genes do not act in isolation, but most models only account for a few features at a time. A systems genetics approach that considers function at a network level permits us to methodically approach the daunting task of connecting heterogeneous genetic risk factors to brain mechanisms (46) (Fig. 4).
