Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA.
Bipolar Disord. 2009 Nov;11(7):701-10. doi: 10.1111/j.1399-5618.2009.00756.x.
Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders.
We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS).
Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL.
Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.
已发表的研究表明，生物钟基因多态性与双相情感障碍 I 型（BPI）以及精神分裂情感障碍（SZA）和精神分裂症（SZ）之间存在关联。基于先前对生物钟异常的研究，这些结果是合理的。由于尚未一致尝试重复，我们评估了所有三种疾病中具有代表性的常见多态性。
我们在 523 名 BPI 患者、527 名 SZ/SZA 患者和 477 名筛选的成年对照组中，检测了 21 个生物钟基因中的 276 个公开的“标记”单核苷酸多态性（SNP）。在与两项已发表的全基因组关联研究（GWAS）相关的情况下，评估了检测到的关联。
使用基于基因的测试，注意到 EGR3 与 BPI 之间存在提示性关联（p = 0.017），以及 NPAS2 与 SZ/SZA 之间存在提示性关联（p = 0.034）。有三个 SNP 与这两种疾病都相关（NPAS2：rs13025524 和 rs11123857；RORB：rs10491929；p < 0.05）。经过多次比较校正后，没有一个关联仍然具有统计学意义。分析中约有 15%的 SNP 与一项针对 BPI 进行 GWAS 的独立研究重叠；在 ARNTL 中，我们注意到 GWAS 分析与我们的分析之间存在提示性重叠。
检测到生物钟基因与 BPI 和 SZ/SZA 之间存在一些提示性的新关联，但目前的分析不支持与风险比大于 1.5 的常见多态性相关联。需要使用足够强大的样本进行额外的分析，以进一步评估这些结果。
