Three recent multicenter studies may have heralded a breakthrough in GWA studies of schizophrenia. None of the initial findings from these three studies surpassed the level of genome-wide significance. However, a meta-analysis of the best hits on European-ancestry data from these three studies and the inbuild replication study by Stefansson et al. identified a cluster of genome-wide significant SNPs in substantial LD in the MHC region on chromosome 6p22.1 (International Schizophrenia Consortium, 2009; Shi et al., 2009; Stefansson et al., 2009). These results may implicate the immunological system in the pathogenesis of schizophrenia. Stefansson et al. (2009) also found that a variant upstream of neurogranin (NRGN; p = 2.4 × 10−9) and a SNP in transcription factor 4 (TCF4; p = 4.1 × 10−9) achieved genome-wide significance. These findings demonstrate that the use of large samples can overcome the limitations in the power of GWA studies to detect common risk variants for complex psychiatric disorders.
