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. 2020 Oct:129:61-65.
doi: 10.1016/j.jpsychires.2020.06.005. Epub 2020 Jun 6.

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

Taku Saito  1 , Hiroyuki Toda  2 , Gabrielle N Duncan  3 , Sydney S Jellison  3 , Tong Yu  3 , Mason J Klisares  3 , Sophia Daniel  3 , Allison J Andreasen  3 , Lydia R Leyden  3 , Mandy M Hellman  3 , Eri Shinozaki  4 , Sangil Lee  5 , Aihide Yoshino  2 , Hyunkeun R Cho  6 , Gen Shinozaki  7
Affiliations

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

Taku Saito et al. J Psychiatr Res. 2020 Oct.

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.

Keywords: Aging; Delirium; Genome-wide DNA methylation; Immune response; Inflammatory response.

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Conflict of interest statement

Conflict of interest

Dr. Shinozaki G is co-founder of Predelix Medical LLC, and reports U.S. Provisional Patent Application No. 62/731599, titled “Epigenetic biomarker of delirium risk.” The other authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Volcano plots: the distribution of individual CpGs and their logarithmic transformed p-values (n = 87)
See this image and copyright information in PMC

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