Meta-analysis of transcriptional regulatory networks for lipid metabolism in neural cells from schizophrenia patients based on an open-source intelligence approach

•Transcriptional networks in the schizophrenia neural cells were reconstructed.•Regulation via enhancers occupied more than half of the edges of the networks.•Meta-analysis revealed commonly used network modules over multiple datasets.•Enrichment of SNPs suggested associations of schizophrenia with...

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Veröffentlicht in:Neuroscience research 2022-02, Vol.175, p.82-97
Hauptverfasser: Okamoto, Lisa, Watanabe, Soyoka, Deno, Senka, Nie, Xiang, Maruyama, Junichi, Tomita, Masaru, Hatano, Atsushi, Yugi, Katsuyuki
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container_issue
container_start_page 82
container_title Neuroscience research
container_volume 175
creator Okamoto, Lisa
Watanabe, Soyoka
Deno, Senka
Nie, Xiang
Maruyama, Junichi
Tomita, Masaru
Hatano, Atsushi
Yugi, Katsuyuki
description •Transcriptional networks in the schizophrenia neural cells were reconstructed.•Regulation via enhancers occupied more than half of the edges of the networks.•Meta-analysis revealed commonly used network modules over multiple datasets.•Enrichment of SNPs suggested associations of schizophrenia with several functions. There have been a number of reports about the transcriptional regulatory networks in schizophrenia. However, most of these studies were based on a specific transcription factor or a single dataset, an approach that is inadequate to understand the diverse etiology and underlying common characteristics of schizophrenia. Here we reconstructed and compared the transcriptional regulatory network for lipid metabolism enzymes using 15 public transcriptome datasets of neural cells from schizophrenia patients. Since many of the well-known schizophrenia-related SNPs are in enhancers, we reconstructed a network including enhancer-dependent regulation and found that 53.3 % of the total number of edges (7,577 pairs) involved regulation via enhancers. By examining multiple datasets, we found common and unique transcriptional modes of regulation. Furthermore, enrichment analysis of SNPs that were connected with genes in the transcriptional regulatory networks by eQTL suggested an association with hematological cell counts and some other traits/diseases, whose relationship to schizophrenia was either not or insufficiently reported in previous studies. Based on these results, we suggest that in future studies on schizophrenia, information on genotype, comorbidities and hematological cell counts should be included, along with the transcriptome, for a more detailed genetic stratification and mechanistic exploration of schizophrenia.
doi_str_mv 10.1016/j.neures.2021.12.006
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There have been a number of reports about the transcriptional regulatory networks in schizophrenia. However, most of these studies were based on a specific transcription factor or a single dataset, an approach that is inadequate to understand the diverse etiology and underlying common characteristics of schizophrenia. Here we reconstructed and compared the transcriptional regulatory network for lipid metabolism enzymes using 15 public transcriptome datasets of neural cells from schizophrenia patients. Since many of the well-known schizophrenia-related SNPs are in enhancers, we reconstructed a network including enhancer-dependent regulation and found that 53.3 % of the total number of edges (7,577 pairs) involved regulation via enhancers. By examining multiple datasets, we found common and unique transcriptional modes of regulation. 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subjects Enhancer
Gene Expression Regulation
Gene Regulatory Networks
Humans
Lipid metabolism
Lipid Metabolism - genetics
Meta-analysis
Open-source intelligence
Schizophrenia
Schizophrenia - genetics
Transcriptional regulatory network
title Meta-analysis of transcriptional regulatory networks for lipid metabolism in neural cells from schizophrenia patients based on an open-source intelligence approach
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