Multimodal analysis of gene expression from postmortem brains and blood identifies synaptic vesicle trafficking genes to be associated with Parkinson's disease
Multimodal analysis of gene expression from postmortem brains and blood identifies synaptic vesicle trafficking genes to be associated with Parkinson's disease
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对死后大脑和血液基因表达的多模式分析确定了与帕金森病相关的突触小泡运输基因
DOI：
10.1093/bib/bbaa244
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发表时间：
2021-07-01
影响因子：
9.5
通讯作者：
Wang, Qing
中科院分区：
文献类型：
--
作者：
Gao, Xiaoya;Huang, Zifeng;Wang, Qing
目的：我们的目的是确定关键易感基因的目标，从死后的大脑和血液的帕金森病（PD）患者和健康对照（HC）生成的多个数据集。方法：我们使用多基因芯片对244例人死后组织的基因表达数据进行了多层次分析。我们通过构建蛋白质-蛋白质相互作用（PPI）网络，在PD高度相关的共识模块中识别出枢纽节点基因。接下来，我们验证了238名受试者（90名散发性PD，125名HC和23名帕金森综合征（PPS））中的前四个相互作用基因。采用多项logistic回归分析（MLRA）和受试者工作特征（ROC）分析PD与HC和PPS的危险因素和诊断能力。结果：基于7个微阵列数据集，我们确定了1333个在PD和HC之间存在显著差异的基因。MEturquoise模块与PD的突触囊泡运输（SVT）功能障碍有关（P < 0.05），PPI分析显示SVT基因PPP 2CA、SYNJ 1、NSF和PPP 3CB是MEturquoise中前4位的枢纽节点基因（P < 0.001）。这四个基因在PD死后脑中的表达水平均低于HC死后脑。PD组PPP 2CA、SYNJ 1和NSF水平均低于HC组，而SYNJ 1水平低于PPS组（P < 0.05）。SYNJ 1与PD的严重程度呈负相关，在区分PD与HC和PPS方面表现出良好的能力。结论：SVT基因，尤其是SYNJ 1基因，可能是区分PD与HC和PPS的一个有前景的标志物。
Objective: We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC). Methods: We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson's Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. Results: We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. Conclusions: This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS.