Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Neurosci Lett. 2012 Oct 31;529(1):66-9. doi: 10.1016/j.neulet.2012.08.070. Epub 2012 Sep 7.
Disturbances of the circadian rhythm are involved in the pathophysiology of bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD). Specifically, because clock gene dysfunction is good candidate for enhancing the susceptibility to these psychiatric disorders, we selected two circadian rhythm-related genes (CSNK1D and CSNK1E) and investigated genetic associations of the genes with these three disorders. None of the SNPs showed a significant association with MDD, but a SNP (rs2075984) in CSNK1E and SNP (rs6502097) in CSNK1D were associated with SCZ (P=0.0091, uncorrected) and BD (P=0.030, uncorrected), respectively. To confirm these findings, we analyzed an independent dataset (maximum N=3815) but found a lack of association (P=0.63 for rs2075984 and P=0.61 for rs6502097). The final meta-analysis showed no association between these SNPs with SCZ (P=0.21) and BD (P=0.53). These results do not support that genetic variation in CSNK1D and CSNK1E is a susceptibility factor for major psychiatric disorders in the Japanese population.
昼夜节律紊乱与双相情感障碍(BD)、精神分裂症(SCZ)和重度抑郁症(MDD)的病理生理学有关。具体而言,由于时钟基因功能障碍是增强这些精神疾病易感性的良好候选因素,我们选择了两个与昼夜节律相关的基因(CSNK1D 和 CSNK1E),并研究了这些基因与这三种疾病的遗传相关性。没有任何 SNP 与 MDD 显著相关,但 CSNK1E 中的 SNP(rs2075984)和 CSNK1D 中的 SNP(rs6502097)与 SCZ(P=0.0091,未校正)和 BD(P=0.030,未校正)相关。为了证实这些发现,我们分析了一个独立的数据集(最大 N=3815),但发现没有关联(rs2075984 的 P=0.63,rs6502097 的 P=0.61)。最终的荟萃分析显示,这些 SNP 与 SCZ(P=0.21)和 BD(P=0.53)之间没有关联。这些结果不支持 CSNK1D 和 CSNK1E 中的遗传变异是日本人群中主要精神疾病的易感因素。