list of the 25 most popular schizophrenia candidate variants including COMT, DISC1, DTNBP1 and NRG1. A liberal interpretation of their findings is that four of the 25 candidate variants they investigated (16%) showed some evidence for association in the Psychiatric Genomics Consortium. In the end, only one of the 25 variants was genome-wide significant. When they expanded their attempt to validate any of the traditional candidate genes to include any variant within the candidate gene of interest, again they found some evidence for association in 4 of 25 genes (16%). The test reported in Farrell et al. makes clear that the traditional approach to candidate gene studies is highly fallible, and the traditional candidate variants within these candidate genes in psychiatry are poor places to search for genetic influences on psychiatric disorder and behavioral traits. Of further note is that Farrell et al. evaluated only the “best” available candidate genes. If one evaluates all of the SCGene database (www.sczgene.org), over 1700 studies have reported over 1000 genes to be associated with schizophrenia, but in this PGC investigation of 150,000 people, the largest and best powered study ever undertaken of schizophrenia genetics, the vast majority of these gene findings could not
