Our knowledge of the genetic architecture of schizophrenia – the number of loci, allele frequencies, genotypic relative risks, and modes of action – has grown significantly in the past year. The largest GWAS to date suggests that schizophrenia is associated with many common genetic variants of small effect sizes. 11 Several rare CNVs have genotypic relative risks in the 5–20 range. 17 Rare exonic variants of stronger effect do play a role, but it now appears unlikely that schizophrenia has a genetic architecture dominated by such variants. 18, 19 A direct comparison found that common genetic variation accounted for far more of the variance in liability to schizophrenia than rare copy number variation or rare deleterious exonic variation.18
