In stage 2, we evaluated in 29,839 independent subjects (8,442 cases and 21,397 controls) the most significant SNPs (N = 81) in each LD region where at least one SNP had surpassed P < 2 × 10−5 (Supplementary Table 6) in the mega-analysis. Of 22 SNPs from the MHC, 5 surpassed the genome-wide significant threshold in stages 1 and 2 combined (minimum P = 2.2 × 10−12 at rs2021722; Supplementary Table 6). Excluding the MHC region, a sign test for consistency between stages 1 and 2 was highly significant (P < 10−6), with the same direction of effect as observed stage 1 also being observed in stage 2 for 49 of 59 SNPs. A Fisher’s combined test revealed the distribution of stage 2 P values was unlikely to have occurred by chance (P < 10−15). We also performed a transmission analysis using the family based Multicenter Pedigree replication sample in conjunction with a GWAS of 622 parent-offspring schizophrenia trios from Bulgaria12, and the stage 1 associated allele was over-transmitted to cases for 44 of the 59 SNPs (one-sided P = 1.0 × 10−4). Thus, the stage 2 replication results are highly consistent with the stage 1 discovery results.
