Table 1.
Candidate genes of historical importance in schizophrenia research
| Gene | Product | Reviews | Pre-GWAS | Rationale |
|---|---|---|---|---|
| AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 2 | 13 | Mood disorder pharmacology 59 |
| APOE | Apolipoprotein E | 1 | 32 | Implicated in Alzheimer’s disease 75 |
| BDNF | Brain-derived neurotrophic factor | 0 | 40 | Neurodevelopment hypothesis 76 |
| CHRNA7 | Cholinergic receptor, nicotinic, α7 | 1 | 12 | Linkage analysis 77 |
| COMT | Catechol-O-methyltransferase | 4 | 81 | 22q11 CNV 78 |
| DAO | D-amino-acid oxidase | 2 | 10 | Linkage analysis, glutamate hypothesis 79 |
| DAOA | D-amino acid oxidase activator | 3 | 27 | Linkage analysis, glutamate hypothesis 79 |
| DISC1 | Disrupted in schizophrenia 1 | 3 | 22 | Translocation in a pedigree 80 |
| DRD2 | Dopamine receptor D2 | 1 | 67 | Antipsychotic pharmacology 81 |
| DRD3 | Dopamine receptor D3 | 2 | 71 | Dopamine hypothesis 20 |
| DRD4 | Dopamine receptor D4 | 0 | 45 | Antipsychotic pharmacology 82 |
| DTNBP1 | Dystrobrevin binding protein 1 | 3 | 32 | Linkage analysis 83 |
| GRM3 | Glutamate receptor, metabotropic 3 | 1 | 15 | Glutamate hypothesis 21 |
| HTR2A | Serotonin receptor 2A | 2 | 57 | Antipsychotic pharmacology 84 |
| KCNN3 | Potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3 | 0 | 23 | Discovery of a CAG repeat 85 |
| MTHFR | Methylenetetrahydrofolate reductase | 0 | 20 | Psychiatric symptoms with MTHFR dysfunction 86 |
| NOTCH4 | Notch 4 | 0 | 24 | Linkage analysis 87 |
| NRG1 | Neuregulin 1 | 3 | 41 | Linkage analysis 88 |
| PPP3CC | Protein phosphatase 3, catalytic subunit, γ isozyme | 1 | 9 | Linkage analysis/mouse phenotype 89 |
| PRODH | Proline dehydrogenase (oxidase) 1 | 3 | 10 | 22q11 CNV (incorrectly called “PRODH2” 90 |
| RGS4 | Regulator of G-protein signaling 4 | 3 | 22 | Differential expression in cases 91 |
| SLC6A3 | Dopamine transporter | 0 | 22 | Dopamine hypothesis 92 |
| SLC6A4 | Serotonin transporter | 1 | 32 | Implicated in mood disorders 93 |
| TNF | Tumor necrosis factor | 0 | 21 | Immune hypothesis 94 |
| ZDHHC8 | Zinc finger, DHHC-type 8 | 2 | 9 | 22q11 CNV 95 |
Reviews: the number of times a gene was in any of four selected reviews of schizophrenia genetics circa 2005. 10, 12–14 Pre-GWAS: the number of schizophrenia candidate gene papers studying this gene in calendar year 2008 or earlier. 2, 16 Rationale: the stated explanation for considering this gene as a candidate gene for schizophrenia according to the original publication. With the exception of DISC1, all studies evaluated common variant hypotheses.