A final crucial point for GWAS studies is that the likely architecture of genetic risk for the psychoses is a matter of considerable debate. Based upon epidemiology, in most cases, risk likely reflects the co-action of several loci but the approximate numbers of loci involved at the individual or the population levels are unknown, as is the spectrum of allele frequencies and effect sizes9,10. At present there is limited direct molecular genetic evidence that favours the existence of common risk alleles. The observations of multiple genome-wide significant or suggestive linkage signals for both disorders that do not readily replicate between studies but which are not randomly distributed across the genome11,12 is compatible with the existence of multiple risk alleles of small-moderate effect. They are not, however, informative with respect to their allele frequencies. Recent papers describing an enrichment of copy number variants in schizophrenia13,14,15 and an excess of de novo CNV events16 in that disorder have raised the possibility of a significant contribution from rare events, some of apparently high penetrance. Whilst it is not yet clear whether the contribution
