The genetic analysis of calcineurin signaling pathway in schizophrenia.

钙调神经磷酸酶级联是神经元信号转导的中心，而这个网络中的基因是耐人寻味的精神分裂症候选易感基因。在这项研究中，我们利用日本精神分裂症家系和病例对照样本进行了钙调神经磷酸酶相关候选基因的关联研究。此外，我们还进行了一项全基因组关联研究，这是一个潜在的强大工具，可以用来识别导致这种疾病的风险变异。我们发现了几个新的疾病候选基因，并揭示了精神分裂症中GABA能通路基因的关联信号积累。此外，我们通过使用精神分裂症患者的死后大脑和候选基因的转基因小鼠来扩展我们的研究。这些发现支持钙调神经磷酸酶/GABA信号的改变与精神分裂症发病机制的遗传关联。

The calcineurin cascade is central to neuronal signal transduction, and genes in this network are intriguing candidate schizophrenia susceptibility genes. In this study, we performed association studies of calcineurin-related candidate genes by using Japanese schizophrenic pedigrees and case-control samples. In addition, we conducted a genome-wide association study (GWAS), which is a potentially powerful tool for identifying the risk variants that underlie the disease. We found several novel candidate genes for the disease, and unveiled the accumulation of association signals from genes of GABAergic pathways in schizophrenia. Furthermore, we extended our study by using postmortem brains of schizophrenic patients and transgenic mice of candidate genes. These findings support the genetic association of altered calcineurin/GABA signaling with schizophrenia pathogenesis.