Table 1b shows current sample sizes and notable findings for the nine PGC working groups. Schizophrenia has accumulated the most data for both common and rare variation. Figure 2b shows significant results from GWAS, copy number variation (CNV), and exome sequencing studies (19, 34, 35). Most findings are for common variation. Multiple rare CNVs have been implicated; most are multi-genic and all increase risk for several psychiatric disorders and neurological diseases (34). SETD1A is the only gene implicated to date by whole exome sequencing studies (35), but other such studies have only found hints of biological pathways by focusing on extremely rare variation (36, 37). It was widely anticipated that exon variation in the 0.005 to 0.01 allele frequency range would be readily found but this has not been observed (38), and a recent study of height required over 700,000 subjects to identify loci in this range (39). In a direct comparison, common variation had 14–28 times more impact on risk for schizophrenia than rare CNVs or rare exonic variation (40).
