We believe the candidate gene design is changing. Instead of basing candidate gene selection on the usual (fallible) suspects (5-HTTLPR, DRD2, DRD4, COMT, BDNF, MAO-A, to name a few), which have largely led to dead ends or confusion, or on results from infrahuman model systems with unknown generalizability, we now know from GWAS what variants are truly associated with human disorders and traits under a controlled family-wise error rate. For schizophrenia, for example, we now have evidence for the association of 128 variants within 108 loci. These “candidate variants” have strong support for their role in schizophrenia and are prima facie good candidates for schizophrenia endophenotypes. In addition, large consortia have formed to identify variants associated with phenotypes other than schizophrenia, such as personality, depression, and educational attainment. Researchers studying endophenotypes related to these distal and clinical outcomes will be able to take advantage of discoveries being made in these areas. The endophenotype then can inform us about the function of those specific markers. For instance, two recently published studies examined a number of these markers now known to be
