Table 1 summarizes 25 historically important candidate genes for schizophrenia. For 24 of 25 genes, the initial study conducted genotyping to evaluate the impact of common genetic variation on risk for schizophrenia. Some candidate genes were selected because of rare genetic events (e.g., COMT, PRODH, and ZDDHC8 are located in the 22q11 deletion CNV) but the study evaluate common genetic variation rather than rare variation. The DISC1 study genotyped rare variation in a Scottish pedigree. The key findings for three genes were unimpressive for schizophrenia per se but presented somewhat more significant findings for putative endophenotypes (CHRNA7 and COMT) or a broadly inclusive set of psychiatric disorders (DISC1). Eleven genes were positional candidates based on genome-wide linkage or structural variation (CHRNA7, COMT, DAO, DAOA, DISC1, DTNBP1, NOTCH4, NRG1, PPP3CC, PRODH, and ZDHHC8). Eight genes derived from a hypothesis about the etiology of schizophrenia based on pharmacology (AKT1, DRD2, DRD3, DRD4, GRM3, HTR2A, SLC6A3, and SLC6A4). Six genes were from miscellaneous hypotheses (APOE, BDNF, KCNN3, MTHFR, RGS4, and TNF).
