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Identification of key genes and pathways for Alzheimer’s disease via combined analysis of genome-wide expression profiling in the hippocampus
Wu Mengsi1,2; Fang Kechi1; Wang Weixiao1,2; Lin Wei1,2; Guo Liyuan1,2; Wang Jing1,2
Contribution Rank1
Abstract

In this study, combined analysis of expression profiling in the hippocampus of 76 patients with Alzheimer’s disease (AD) and 40 healthy controls was performed. The effects of covariates (including age, gender, postmortem interval, and batch effect) were controlled, and differentially expressed genes (DEGs) were identified using a linear mixed-effects model. To explore the biological processes, functional pathway enrichment and protein-protein interaction (PPI) network analyses were performed on the DEGs. The extended genes with PPI to the DEGs were obtained. Finally, the DEGs and the extended genes were ranked using the convergent functional genomics method. Eighty DEGs with q\0.1, including 67 downregulated and 13 upregulated genes, were identified. In the pathway enrichment analysis, the 80 DEGs were significantly enriched in one Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, GABAergic synapses, and 22 Gene Ontology terms. These genes were mainly involved in neuron, synaptic signaling and transmission, and vesicle metabolism. These processes are all linked to the pathological features of AD, demonstrating that the GABAergic system, neurons, and synaptic function might be affected in AD. In the PPI network, 180 extended genes were obtained, and the hub gene occupied in the most central position was CDC42. After prioritizing the candidate genes, 12 genes, including five DEGs (ITGB5, RPH3A, GNAS, THY1, and SEPT6) and seven extended genes (JUN, GDI1, GNAI2, NEK6, UBE2D3, CDC42EP4, and ERCC3), were found highly relevant to the progression of AD and recognized as promising biomarkers for its early diagnosis.

KeywordAlzheimer’s disease Combined analysis Hippocampus Gene expression Differentially expressed genes Microarray
2019
DOIhttp://dx.doi.org/10.1007/s41048-019-0086-2
Source PublicationBiophysics Reports
ISSN2364-3439
Volume5Issue:2Pages:98-109
Subtype实证研究
URL查看原文
Indexed ByCSCD
PublisherSpringer Nature B.V.
CSCD IDCSCD:6498231
DisordersAlzheimer
Number of Participants76 patients with Alzheimer’s disease (AD) ; 40 healthy controls
Country or RegionChina
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Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/33988
Collection中国科学院心理健康重点实验室
Affiliation1.Chinese Academy of Sciences, CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China
2.University of Chinese Academy of Sciences, Department of Psychology, Beijing, China
First Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
Wu Mengsi,Fang Kechi,Wang Weixiao,等. Identification of key genes and pathways for Alzheimer’s disease via combined analysis of genome-wide expression profiling in the hippocampus[J]. Biophysics Reports,2019,5(2):98-109.
APA Wu Mengsi,Fang Kechi,Wang Weixiao,Lin Wei,Guo Liyuan,&Wang Jing.(2019).Identification of key genes and pathways for Alzheimer’s disease via combined analysis of genome-wide expression profiling in the hippocampus.Biophysics Reports,5(2),98-109.
MLA Wu Mengsi,et al."Identification of key genes and pathways for Alzheimer’s disease via combined analysis of genome-wide expression profiling in the hippocampus".Biophysics Reports 5.2(2019):98-109.
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