Table 3. . Replicated genome-wide significant loci.
| Gene | Location | Gene function/significance | SNP | p-value | Study | Ref. |
|---|---|---|---|---|---|---|
| CNTNAP5 | 2q14.3 | • Protein is highly expressed in myelinated neurons • Involved in generation of action potentials • Implicated in GWAS of bipolar disorder |
rs12711680 | 2.12 × 10-8 | Yu et al. | [26] |
| rs4848939 | 3.79 × 10-7 | Yu et al. | [26] | |||
| rs17727261 | 5.4 × 10-7 | McClay et al. | [11] | |||
| GRM7 | 3p26.1 | • Encodes a metabotropic glutamate receptor • Plays a critical role in glutamate regulation • Implicated in schizophrenia and bipolar disorder |
rs2133450 | 4.33 × 10-8 | Sacchetti et al., CATIE trial‡ | [17] |
| rs2069062 | < 0.04 | Stevenson et al. | [16] | |||
| rs1532544 | < 0.04 | Stevenson et al. | [16] | |||
| rs1156328 | 4.50 × 10-5 | Yu et al. | [26] | |||
| TNIK | 3q26.2 | • Encodes a kinase that also has scaffolding properties • Modulates concentrations of GRIA1 at the cellular surface • Interacts with DISC1, a known schizophrenia risk marker |
rs6444970 | 4.85 × 10-8 | Yu et al. | [26] |
| rs2088885 | 0.035 | Xu et al. | [36] | |||
| PCDH7 | 4p15.1 | • Encodes a membrane-bound protein involved in cell adhesion • Modulates signal transduction of the dopamine D1 receptor |
rs9291547 | 3.24 × 10-9 | Yu et al. | [26] |
| rs77685948 | 6.69 × 10-8 | Yu et al. | [26] | |||
| rs17390445 | 9.8 × 10-8 | McClay et al. | [11] | |||
| rs17390445 | 0.02 | Li et al. | [20] | |||
| rs11722719 | 5.4 × 10-7 | McClay et al. | [11] | |||
| rs11722719 | 0.0015 | Li et al. | [20] | |||
| GRID2 | 4q22.2 | • Encodes an ionotropic glutamate receptor • Mediates excitatory synaptic transmission • Implicated in risk for OCD and psychosis |
rs9307122 | 1.10 × 10-8 | Stevenson et al. | [16] |
| rs1875705 | 1.10 × 10-8 | Stevenson et al. | [16] | |||
| rs76800659† | 5.10 × 10-4 | Yu et al. | [26] | |||
| rs3775003 | 2.20 × 10-4 | Ikeda et al. | [9] | |||
| KCNK9 | 8q24.3 | • Encodes a leak potassium channel • Plays a critical role in setting resting membrane potential and repolarizing neurons • 8q24 region has been heavily implicated in neuropsychiatric disorders |
rs4736253 | 4.78 × 10-8 | Li et al. | [20,21] |
| rs2288687 | 4.79 × 10-6 | Stevenson et al. | [16] | |||
| rs1992525 | 1.41 × 10-6 | Stevenson et al. | [16] | |||
| rs6981424 | 1.04 × 10-5 | Stevenson et al. | [16] | |||
| rs687279 | 2.89 × 10-6 | Stevenson et al. | [16] | |||
| SLC1A1 | 9p24.2 | • Encodes the glutamate reuptake transporter • Implicated in risk for OCD, antipsychotic-induced OCD and schizophrenia • Expression is decreased following chronic antipsychotic treatment in animals |
rs1471786 | 2.33 × 10-9 | Yu et al. | [26] |
| rs301440§ | 2.03 × 10-7 | Yu et al. | [26] | |||
| rs10974671 | 0.0035 | Stevenson et al. | [16] | |||
Replication defined as exceeding GWAS significance in one study and achieving at least nominal significance in a second.
†In perfect LD with rs1875705.
‡Sacchetti et al. validated this finding in a secondary analysis of the CATIE dataset.
§In the nearby SPATA6L gene.
CATIE: Clinical antipsychotic trials of intervention effectiveness; GWAS: Genome-wide association studies; LD: Linkage disequilibrium; OCD: Obsessive–compulsive disorder.