in general, the common risk alleles identified by GWAS have small effect sizes (OR<1.25), although the associated allele at ANK3 may have a somewhat larger, but still weak effect (OR~1.45) (27). It is, however, clear that many more common risk alleles remain to be identified, a substantial component (at least 30%) of the variance in risk of schizophrenia being attributable to risk alleles of very small effect, and many of these also influence risk of bipolar disorder (5). In the case of schizophrenia, several rare susceptibility CNVs have also been detected; in contrast to common alleles, these have fairly large effect sizes (OR>3) on disease risk. However, like the common alleles, these CNVs are not specific to individual disorders as defined by widely used classification systems; the same CNVs associated with schizophrenia additionally influence risk of other neurodevelopmental disorders such as autism, epilepsy, and mental retardation(12). Although very little of the genetic risk of either schizophrenia or bipolar disorder is currently explained, there are grounds for optimism that larger studies will reveal more about the origins of these disorders. Moreover, the existing findings already challenge current concepts of disease classification (9) and point to some pathophysiological mechanisms, for example the
