Brain expressed microRNAs implicated in schizophrenia etiology.
Brain expressed microRNAs implicated in schizophrenia etiology.
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大脑表达的microRNA与精神分裂症病因有关。
DOI：
10.1371/journal.pone.0000873
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发表时间：
2007-09-12
期刊：
影响因子：
3.7
通讯作者：
Werge, Thomas
中科院分区：
文献类型：
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作者：
Hansen, Thomas;Olsen, Line;Lindow, Morten;Jakobsen, Klaus D.;Ullum, Henrik;Jonsson, Erik;Andreassen, Ole A.;Djurovic, Srdjan;Melle, Ingrid;Agartz, Ingrid;Hall, Hakan;Timm, Sally;Wang, August G.;Werge, Thomas
蛋白质编码基因一直是精神分裂症遗传学研究的主要目标。然而，随着对调节性microRNAs（miRNAs）在脑发育和功能中的重要性的鉴定，miRNAs基因已成为精神分裂症相关遗传因子的候选基因。事实上，对miRNA在分子和细胞机制上的调节特性和多效性效应的日益了解表明，miRNA与其mRNA靶点之间相互作用的改变可能有助于表型变异。我们研究了精神分裂症和与脑表达相关的miRNA基因的遗传变异之间的关联，采用病例对照研究设计，对三个斯堪的纳维亚样本进行研究。分析了三个样本（丹麦，瑞典和挪威：420/163/257名精神分裂症患者和1006/177/293名对照受试者）中脑表达miRNA内或附近的18个已知SNP。随后，对显示边缘关联的SNP进行三个样品的联合分析。hsa-mir-206（mir-206）和hsa-mit-198（mir-198）中的两个SNPs rs 17578796和rs 1700分别在丹麦和挪威样本中显示出与精神分裂症的名义上显著的等位基因关联（P = 0.0021 & p = 0.038），其中只有rs 17578796在联合样本中是显著的。 计算机模拟分析显示，在15个被预测为受mir-206和mir-198调控的基因中，有8个是JUN、ATF 2和TAF 1的转录靶点或相互作用伙伴，它们连接在一个紧密的网络中。JUN和网络中的两个miRNA靶点（CCND 2和PTPN 1）以前与精神分裂症有关。我们发现脑表达的miRNAs与精神分裂症之间存在名义上的关联，rs 17578796和rs 1700分别位于mir-206和mir-198。这两种miRNAs具有惊人的大量（15个）共同靶点，其中8个也由相同的转录因子连接。
Protein encoding genes have long been the major targets for research in schizophrenia genetics. However, with the identification of regulatory microRNAs (miRNAs) as important in brain development and function, miRNAs genes have emerged as candidates for schizophrenia-associated genetic factors. Indeed, the growing understanding of the regulatory properties and pleiotropic effects that miRNA have on molecular and cellular mechanisms, suggests that alterations in the interactions between miRNAs and their mRNA targets may contribute to phenotypic variation. We have studied the association between schizophrenia and genetic variants of miRNA genes associated with brain-expression using a case-control study design on three Scandinavian samples. Eighteen known SNPs within or near brain-expressed miRNAs in three samples (Danish, Swedish and Norwegian: 420/163/257 schizophrenia patients and 1006/177/293 control subjects), were analyzed. Subsequently, joint analysis of the three samples was performed on SNPs showing marginal association. Two SNPs rs17578796 and rs1700 in hsa-mir-206 (mir-206) and hsa-mit-198 (mir-198) showed nominal significant allelic association to schizophrenia in the Danish and Norwegian sample respectively (P = 0.0021 & p = 0.038), of which only rs17578796 was significant in the joint sample. In-silico analysis revealed that 8 of the 15 genes predicted to be regulated by both mir-206 and mir-198, are transcriptional targets or interaction partners of the JUN, ATF2 and TAF1 connected in a tight network. JUN and two of the miRNA targets (CCND2 and PTPN1) in the network have previously been associated with schizophrenia. We found nominal association between brain-expressed miRNAs and schizophrenia for rs17578796 and rs1700 located in mir-206 and mir-198 respectively. These two miRNAs have a surprising large number (15) of targets in common, eight of which are also connected by the same transcription factors.
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影响因子：
56.9
作者：
Cheng, J;Kapranov, P;Gingeras, TR
通讯作者：
Gingeras, TR
影响因子：
5.2
作者：
Krichevsky, Anna M.;Sonntag, Kai-C.;Kosik, Kenneth S.
通讯作者：
Kosik, Kenneth S.
影响因子：
4.5
作者：
Davidsson, P;Gottfries, J;Blennow, K
通讯作者：
Blennow, K
影响因子：
4.7
作者：
Lugli, G;Larson, J;Smalheiser, NR
通讯作者：
Smalheiser, NR
DOI：
10.1101/sqb.2003.68.69
发表时间：
2003-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Fan, JB;Oliphant, A;Chee, MS
通讯作者：
Chee, MS