Third, we identified a set of loci that have opposite effects on risk of psychiatric disorders. Notably, these included loci with opposing effects on pairs of disorders that are genetically correlated and have common clinical features. For example, a SNP within MRSA was associated with opposing effects on two neurodevelopmental disorders (ASD and SCZ), and a variant within KIAA1109 had opposite directional effects on major mood disorders (BIP and MD) (Table S3.3). These results underscore the complexity of genetic relationships among related disorders and suggest that overall genetic correlations may obscure a more complex set of genetic relationships at the level of specific loci and pathways, as seen in immune-mediated diseases (Baurecht et al., 2015; Lettre and Rioux, 2008; Schmitt et al., 2016). This heterogeneity of effects between genetically correlated disorders is also consistent with a recent analysis that revealed loci contributing to biological differences between BIP and SCZ and found polygenic risk score associations with specific symptom dimensions (Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2018). A complete picture of cross-phenotype genetic relationships will require
