In sum, in a large-scale cross-disorder genome-wide meta-analysis, we identified three genetic factors underlying the genetic basis of eight psychiatric disorders. We also identified 109 genomic loci with pleiotropic effects, of which 33 have not previously been associated with any of the individual disorders. In addition, we identified 11 loci with opposing directional effects on two or more psychiatric disorders. These results highlight disparities between our clinically-defined classification of psychiatric disorders and underlying biology. Future research is warranted to determine whether more genetically-defined influences on cross-diagnostic traits or subtypes of dissect may inform a biologically-informed reconceptualization of psychiatric nosology. Finally, we found that genes associated with multiple psychiatric disorders are disproportionately associated with biological pathways related to neurodevelopment and exhibit distinctive gene expression patterns, with enhanced expression beginning in the second prenatal trimester and persistently elevated expression relative to less pleiotropic genes. Therapeutic modulation of pleiotropic gene products could have broad-spectrum effects on psychopathology.
