We acknowledge the advantages of hindsight. The hypothesis-driven candidate gene literature, a body of work to which the present authors have contributed, contains numerous studies that were state-of-the-art when they were done and represent considerable effort by teams of investigators. GWAS will undoubtedly be subject to similar scrutiny as that done here for candidate gene studies. Although the ISC is the largest and most comprehensive schizophrenia GWAS published to date, it still was not ideal. Although statistical power was high by historical standards, we now know that greater power is desirable to detect the small genotypic relative risks characteristic of schizophrenia. In addition, coverage was not necessarily “genome-wide” as some important regions had inadequate genotyping and rare genetic variation was poorly assessed. With these caveats in mind, a number of observations of the historical candidate gene literature emerged from our analyses.
