Epigenetics of neuroinflammation: Immune response, inflammatory response and cholinergic synaptic involvement evidenced by genome-wide DNA methylation analysis of delirious inpatients

Taku Saito; Hiroyuki Toda; Gabrielle N Duncan; Sydney S Jellison; Tong Yu; Mason J Klisares; Sophia Daniel; Allison J Andreasen; Lydia R Leyden; Mandy M Hellman; Eri Shinozaki; Sangil Lee; Aihide Yoshino; Hyunkeun R Cho; Gen Shinozaki

doi:10.1016/j.jpsychires.2020.06.005

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Epigenetics of neuroinflammation: Immune response, inflammatory response and cholinergic synaptic involvement evidenced by genome-wide DNA methylation analysis of delirious inpatients

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Epigenetics of neuroinflammation: Immune response, inflammatory response and cholinergic synaptic involvement evidenced by genome-wide DNA methylation analysis of delirious inpatients

Taku Saito, Hiroyuki Toda, Gabrielle N Duncan, Sydney S Jellison, Tong Yu, Mason J Klisares, Sophia Daniel, Allison J Andreasen, Lydia R Leyden, Mandy M Hellman, …

Journal of psychiatric research, Vol.129, pp.61-65

10/2020

DOI: 10.1016/j.jpsychires.2020.06.005

PMID: 32590150

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Abstract

Previously our study has shown that the DNA methylation (DNAm) levels at CpG sites in the pro-inflammatory cytokine gene, TNF-alpha, decrease along with aging, suggesting the potential role of DNAm in aging and heightened inflammatory process leading to increased risk for delirium. However, DNAm differences between delirium cases and non-delirium controls have not been investigated directly. Therefore, we examined genome-wide DNAm differences in blood between patients with delirium and controls to identify useful epigenetic biomarkers for delirium. Data from a total of 87 subjects (43 delirium cases) were analyzed by a genome-wide DNAm case-control association study. A genome-wide significant CpG site near the gene of LDLRAD4 was identified (p = 5.07E-8). In addition, over-representation analysis showed several significant pathways with a false discovery rate adjusted p-value < 0.05. The top pathway with a Gene Ontology term was immune response, and the second top pathway with a Kyoto Encyclopedia of Genes and Genomes term was cholinergic synapse. Significant DNAm differences related to immune/inflammatory response were shown both at gene and pathway levels between patients with delirium and non-delirium controls. This finding indicates that DNAm status in blood has the potential to be used as epigenetic biomarkers for delirium. •A genome-wide significant CpG site near the gene of LDLRAD4 was identified from the genome-wide DNAm investigation of delirium.•Several significant pathways related to immune/inflammatory response/cholinergic function were identified.•DNA methylation status in blood may be used as epigenetic biomarkers for delirium.

Aging

Delirium

Inflammatory response

Immune response

Genome-wide DNA methylation

Details

Title: Subtitle: Epigenetics of neuroinflammation: Immune response, inflammatory response and cholinergic synaptic involvement evidenced by genome-wide DNA methylation analysis of delirious inpatients
Creators: Taku Saito - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Hiroyuki Toda - Department of Psychiatry, School of Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan
Gabrielle N Duncan - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Sydney S Jellison - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Tong Yu - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Mason J Klisares - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Sophia Daniel - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Allison J Andreasen - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Lydia R Leyden - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Mandy M Hellman - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Eri Shinozaki - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Sangil Lee - Department of Emergency Medicine, University of Iowa, Iowa City, IA, USA
Aihide Yoshino - Department of Psychiatry, School of Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan
Hyunkeun R Cho - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA
Gen Shinozaki - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Journal of psychiatric research, Vol.129, pp.61-65
DOI: 10.1016/j.jpsychires.2020.06.005
PMID: 32590150
NLM abbreviation: J Psychiatr Res
ISSN: 0022-3956
eISSN: 1879-1379
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100008893, name: University of Iowa
Language: English
Date published: 10/2020
Academic Unit: Psychiatry; Emergency Medicine; Iowa Neuroscience Institute; Biostatistics; Anesthesia; Injury Prevention Research Center; General Internal Medicine; Neurosurgery; Otolaryngology; Internal Medicine
Record Identifier: 9984070459502771

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