Association study of clock gene (CLOCK) and schizophrenia and mood disorders in the Japanese population
Association study of clock gene (CLOCK) and schizophrenia and mood disorders in the Japanese population
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DOI：
10.1007/s00406-009-0869-4
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发表时间：
2009-08-01
影响因子：
4.7
通讯作者：
Iwata, Nakao
中科院分区：
文献类型：
--
作者：
Kishi, Taro;Kitajima, Tsuyoshi;Iwata, Nakao
最近有报道称，生物钟基因在神经递质系统（包括多巴胺系统）中发挥一定作用，并调节昼夜节律。这两种机制的异常被认为与主要精神疾病的病理生理学有关，如精神分裂症和心境障碍，包括双相情感障碍（BP）和重度抑郁症（MDD）。最近的遗传学研究报道，时钟基因之一的CLOCK与这些精神疾病有关。因此，我们研究了CLOCK中的6个标签SNP与诊断为精神分裂症（733例患者）、BP（149例）和MDD（324例）的日本患者以及795名日本对照者中这些精神疾病风险之间的关联。在单倍型分析中仅检测到一个与女性精神分裂症的关联（P = 0.0362）。然而，在Bonferroni校正后，这种显著性并不存在（P = 0.0724）。未发现与BP和MDD的显著相关性。总之，我们认为，时钟可能不会发挥重要作用，在日本精神分裂症，BP和MDD患者的病理生理。然而，重要的是在其他使用大样本的独立研究中复制和确认这些发现。
Recently the clock genes have been reported to play some roles in neural transmitter systems, including the dopamine system, as well as to regulate circadian rhythms. Abnormalities in both of these mechanisms are thought to be involved in the pathophysiology of major mental illness such as schizophrenia and mood disorders including bipolar disorder (BP) and major depressive disorder (MDD). Recent genetic studies have reported that CLOCK, one of the clock genes, is associated with these psychiatric disorders. Therefore, we investigated the association between the six tagging SNPs in CLOCK and the risk of these psychiatric disorders in Japanese patients diagnosed with schizophrenia (733 patients), BP (149) and MDD (324), plus 795 Japanese controls. Only one association, with schizophrenia in females, was detected in the haplotype analysis (P = 0.0362). However, this significance did not remain after Bonferroni correction (P = 0.0724). No significant association was found with BP and MDD. In conclusion, we suggest that CLOCK may not play a major role in the pathophysiology of Japanese schizophrenia, BP and MDD patients. However, it will be important to replicate and confirm these findings in other independent studies using large samples.