Selecting “candidate” genes has long been practiced in behavioral and psychiatric genetic research. Candidate gene often really means candidate variant, where a particular genotype within a gene is selected typically on the basis of functional studies in model organisms. One conclusion from GWAS has now been clear for some time – the expected effect size for such popular polymorphisms are no larger than effect sizes identified by GWAS. Even if a candidate polymorphism is truly associated with a phenotype, it will be at levels difficult to detect without a highly powered design. A recent intriguing test of the candidate gene design is reported in a paper by Farrell et al. (2015) in which the authors cross-referenced 108 schizophrenia-significant loci discovered by the Psychiatric Genomics Consortium (PGC) (Kamarajan & Porjesz, 2015; Schizophrenia Working Group of the Psychiatric Genomics, 2014) with a 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
