Table I.
Summary of 15 Circadian Genes Tested for Association with Bipolar Disorder
| Gene | Protein function | Location | Length (kb)a | SNPs typed |
|---|---|---|---|---|
| Sample I | ||||
| CRY2: cryptochrome 2 | Inhibition of CLOCK-BMAL1 | 11p11.2 | 55.8 | 4 |
| PER1: period1 | Inhibition of CLOCK-BMAL1 | 17p13.1-17p12 | 31.9 | 3 |
| PER2: period2 | Inhibition of CLOCK-BMAL1 | 2q37.3 | 64.4 | 3 |
| PER3: period3 | Association with CRY? | 1p36.23 | 80.5 | 5 |
| TIMELESS: timeless homolog (Drosophila) | Interaction with PER1 and inhibition of CLOCK-BMAL1-induced transactivation | 12q12-q13 | 52.2 | 4b |
| Sample II | ||||
| ARNTL: aryl hydrocarbon receptor nuclear translocator-like ( BMAL1; MOP3) | Activation of CLOCK and CLOCK-controlled genes (with CLOCK) | 11p15 | 129.5 | 14 |
| ARNTL2: aryl hydrocarbon receptor nuclear translocator-like 2 (BMAL2) | Activation of CLOCK and CLOCK-controlled genes? | 12p12.2-p11.2 | 107.5 | 13 |
| BHLHB2: basic helix-loop-helix domain containing, class B, 2 | Inhibition of CLOCK-BMAL1-induced transactivation of PER1 | 3p26 | 25.7 | 4 |
| BHLHB3: basic helix-loop-helix domain containing, class B, 3 | Inhibition of CLOCK-BMAL1-induced transactivation of PER1 | 12P11-12 | 24.9 | 3 |
| CLOCK: circadian locomoter output cycles protein kaput | Activation of CLOCK and CLOCK-controlled genes with BMAL1) | 4q12 | 134.3 | 6 |
| CRY1: cryptochrome 1 | Inhibition of CLOCK-BMAL1 | 12q23-q24.1 | 122.2 | 4 |
| CSNK1D: casein kinase 1, delta | Phosphorylation of PERs, CRYs and BMAL1 | 17q25 | 49.3 | 3 |
| CSNK1E: casein kinase 1, epsilon | Phosphorylation of PERs, CRYs and BMAL1 | 22q13.1 | 47.4 | 9 |
| DBP: D site of albumin promoter binding protein | Output, activation of PER1? | 19q13.3 | 26.6 | 2 |
| NR1D1: nuclear receptor subfamily 1, group D, member 1 (REVERBA) | Inhibition of BMAL1 | 17q11.2 | 27.9 | 4 |
a
Genic sequence (NCBI B35) and 10 kb upstream and downstream.
b
Two SNPs (rs2291738 and rs10876890) were found to be associated with insomnia during mania episode in bipolar disorder patients in CNG and waves 1–2 samples, and then were genotyped in CHIP and waves 3–4 samples; other two SNPs (rs774026 and rs2279665), which showed suggestive association evidence with bipolar disorder by Mansour HA et al, were genotyped in CHIP, CNG, and NIMH waves 1–4 samples. These four SNPs were typed using TaqMan assays.