Fifth, our analyses of spatiotemporal gene expression profiles revealed that pleiotropic loci are enriched among genes expressed in neuronal cell types, particularly in frontal or prefrontal regions. They also demonstrated a distinctive feature of genes related to pleiotropic loci: compared with disorder-specific loci, they are on average expressed at higher levels both prenatally and postnatally (Figure 5). More specifically, single-disorder (mainly SCZ) loci were related to genes that were preferentially expressed in the first fetal trimester followed by a decline over the prenatal period and then relatively stable levels postnatally. In contrast, average expression of genes related to pleiotropic loci peaked in the second trimester and remained overexpressed throughout the lifespan. When dividing the pleiotropic loci into bins of those associated with two disorders (mainly SCZ and BIP) vs. three or more disorders, we observed a consistent gradient of greater expression associated with broader pleiotropy. These results are based on average expression profiles, and not all individual gene expression patterns follow this pattern.
