Clinical, epidemiological and genetic findings suggest shared risk factors between bipolar disorder and schizophrenia29. In stage 1, three genes with strong support had prior genome-wide significant associations with bipolar disorder: CACNA1C, the region containing ITIH3-ITIH4 (encoding inter-α (globulin) inhibitors H3 and H4) and ANK3 (encoding ankyrin 3, node of Ranvier (ankyrin G))10,11,30 (Supplementary Table 10). We performed a joint analysis with the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC) for bipolar disorder applying identical analytical methods. After removing duplicate subjects, we analyzed 16,374 cases with schizophrenia, schizoaffective disorder or bipolar disorder and 14,044 controls. Support for shared susceptibility was strengthened (Supplementary Table 11) at CACNA1C (rs4765905, P = 7.0 × 10−9), ANK3 (rs10994359, P = 2.5 × 10−8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10−9), each of which reached genome-wide significance. A coding variant in ITIH4 (p.Pro698Thr; rs4687657) is in perfect LD with the most associated SNP. Although we included all subjects from an earlier report10, the increased support found with additional independent cases (N = 11,987) and controls (N = 7,835) provides further evidence for shared risk effects of schizophrenia and bipolar disorder.
