Our prior cross-disorder meta-analysis of five psychiatric disorders (Cross-Disorder Group of the Psychiatric Genomics Consortium, 2013) found no evidence of SNPs with antagonistic effects on two or more disorders. Here, we examined whether any variants with meta-analysis p ≤ 1×10−6 had opposite directional effects between disorders (Online Methods). After adjusting for having examined 206 loci across eight disorders (q < 0.001), we identified 11 loci with evidence of opposite directional effects on two or more disorders (Fig. 4; Table S3.3). The disorder configuration of opposite directional effects varied for the 11 loci, including three loci with opposite directional effects on SCZ and MD (rs301805, rs1933802, rs3806843), two loci between SCZ and ASD (rs9329221, rs2921036), and one locus (rs75595651) with opposite directional effects on the two mood disorders, BIP and MD. Notably, all of the six loci involving SCZ and BIP exhibited the same directional effect on the two disorders (Pbinom < 0.05), in line with their strong genome-wide genetic correlation.
