The genetic analysis of calcineurin signaling pathway in schizophrenia.

精神分裂症钙调神经磷酸酶信号通路的遗传分析。

• 批准号: 20390316
• 负责人: YAMADA Kazuo
• 金额: $ 12.23万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390316/
• 关键词: 脳・神経疾患; 遺伝子; シグナル伝達; ゲノム; マイクロアレイ

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.

钙调神经素级联对于神经元信号转导至关重要，该网络中的基因是吸引人的精神分裂症易感基因。在这项研究中，我们通过使用日本精神分裂症和病例对照样本对钙调神经素相关的候选基因进行了关联研究。此外，我们进行了全基因组关联研究（GWAS），该研究是识别疾病构成的风险变异的潜在强大工具。我们发现了该疾病的几个新型候选基因，并揭示了精神分裂症中GABA能途径基因的关联信号的积累。此外，我们通过使用精神分裂症患者和候选基因的转基因小鼠的后大脑扩展了研究。这些发现支持改变的钙调神经/GABA信号传导与精神分裂症发病机理的遗传关联。

项目成果

Failure to Confirm Genetic Association of the CHI3L1 Gene With Schizophrenia in Japanese and Chinese Populations

• DOI: 10.1002/ajmg.b.30847
• 发表时间: 2009-06-05
• 期刊: AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
• 影响因子: 2.8
• 作者: Yamada, Kazuo;Hattori, Eiji;Yoshikawa, Takeo
• 通讯作者: Yoshikawa, Takeo

Genetic architecture that defines endphenotypes in mice and its molecular relevance to mental disorders.

定义小鼠终表型的遗传结构及其与精神障碍的分子相关性。

• 发表时间: 2008
• 作者: K.Ogawa;Y.Ozaku;Y.Nyui;M.Fukushi;Yoshikawa T
• 通讯作者: Yoshikawa T

Toward Genetics Dissection of Psychiatric Illnesses.

精神疾病的遗传学剖析。

• 发表时间: 2008
• 作者: K.Ogawa;Y.Ozaku;Y.Nyui;M.Fukushi;Yoshikawa T;Takeo Yoshikawa;Yoshikawa T
• 通讯作者: Yoshikawa T

Toward Genetics Dissection of Psychiatric Illnesses

精神疾病的遗传学剖析

• 发表时间: 2008
• 作者: K.Ogawa;Y.Ozaku;Y.Nyui;M.Fukushi;Yoshikawa T;Takeo Yoshikawa;Yoshikawa T;Takeo Yoshikawa
• 通讯作者: Takeo Yoshikawa

Mitochondrial DNA Haplogroup Analysis in Patients With Bipolar Disorder

• DOI: 10.1002/ajmg.b.30804
• 发表时间: 2009-03-05
• 期刊: AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
• 影响因子: 2.8
• 作者: Kazuno, An-a;Munakata, Kae;Kato, Tadafumi
• 通讯作者: Kato, Tadafumi