Genome-wide DNA methylation analysis of post-operative delirium with brain, blood, saliva, and buccal samples from neurosurgery patients

Nadia E. Wahba; Yoshitaka Nishizawa; Pedro S. Marra; Takehiko Yamanashi; Kaitlyn J. Crutchley; Takaaki Nagao; Kazuki Shibata; Tsuyoshi Nishiguchi; Hyunkeun Cho; Mathew A. Howard; Hiroto Kawasaki; Marco Hefti; Tetsufumi Kanazawa; Gen Shinozaki

doi:10.1016/j.jpsychires.2022.10.023

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Genome-wide DNA methylation analysis of post-operative delirium with brain, blood, saliva, and buccal samples from neurosurgery patients

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Genome-wide DNA methylation analysis of post-operative delirium with brain, blood, saliva, and buccal samples from neurosurgery patients

Nadia E. Wahba, Yoshitaka Nishizawa, Pedro S. Marra, Takehiko Yamanashi, Kaitlyn J. Crutchley, Takaaki Nagao, Kazuki Shibata, Tsuyoshi Nishiguchi, Hyunkeun Cho, Mathew A. Howard, …

Journal of psychiatric research, Vol.156, pp.245-251

12/2022

DOI: 10.1016/j.jpsychires.2022.10.023

PMCID: PMC10540238

PMID: 36270064

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https://pmc.ncbi.nlm.nih.gov/articles/PMC10540238/pdf/nihms-1929617.pdfView

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Abstract

No previous study demonstrates the difference in the genome-wide DNA methylation status of post-operative delirium (POD) using human brain tissue obtained from neurosurgery and multiple peripheral tissues such as blood, saliva, and buccal samples from the same individuals. We aimed to identify epigenetic marks of DNA methylation in the brain and peripheral tissues to elucidate the potential pathophysiological mechanism of POD. The four tissue types (brain, blood, saliva, buccal) of DNA samples from up to 40 patients, including 11 POD cases, were analyzed using Illumina EPIC array. DNAm differences between patients with and without POD were examined. We also conducted enrichment analysis based on the top DNAm signals. The most different CpG site between control and POD was found at cg16526133 near the ADAMTS9 gene from the brain tissue(p = 8.66E-08). However, there are no CpG sites to reach the genome-wide significant level. The enrichment analysis based on the 1000 top hit CpG site (p < 0.05) on the four tissues showed several intriguing pathways. In the brain, there are pathways including “positive regulation of glial cell differentiation”. Blood samples showed also pathways related to immune function. Besides, both saliva and the buccal sample showed pathways related to circadian rhythm, although these findings were not FDR significant. Enrichment analysis found several intriguing pathways related to potential delirium pathophysiology. Present data may further support the role of epigenetics, especially DNA methylation, in the molecular mechanisms of delirium pathogenesis. •This study is the first genome-wide DNA methylation association study of postoperative delirium using human brain tissue and peripheral tissues such as blood, saliva, and buccal samples.•Enrichment analysis based on brain tissue showed pathways related to glia, and blood tissue showed pathways related to immune function.•Analysis based on saliva and buccal tissue showed circadian rhythm pathways.•Present data may support the potential role of epigenetics in the molecular mechanisms of delirium pathogenesis.

Epigenetics

Neurosurgery

Delirium

DNA methylation

Genome-wide

Post-operative delirium

Details

Title: Subtitle: Genome-wide DNA methylation analysis of post-operative delirium with brain, blood, saliva, and buccal samples from neurosurgery patients
Creators: Nadia E. Wahba - University of Iowa
Yoshitaka Nishizawa - Stanford University School of Medicine
Pedro S. Marra - University of Iowa Carver College of Medicine, Department of Psychiatry, Iowa City, IA, USA
Takehiko Yamanashi - University of Iowa
Kaitlyn J. Crutchley - University of Iowa
Takaaki Nagao - Toho University
Kazuki Shibata - Stanford University School of Medicine
Tsuyoshi Nishiguchi - Stanford University School of Medicine
Hyunkeun Cho - University of Iowa College of Public Health, Department of Biostatistics, Iowa City, IA, USA
Mathew A. Howard - University of Iowa Carver College of Medicine, Department of Neurosurgery, Iowa City, IA, USA
Hiroto Kawasaki - University of Iowa Carver College of Medicine, Department of Neurosurgery, Iowa City, IA, USA
Marco Hefti - University of Iowa
Tetsufumi Kanazawa - Osaka Medical and Pharmaceutical University
Gen Shinozaki - University of Iowa
Resource Type: Journal article
Publication Details: Journal of psychiatric research, Vol.156, pp.245-251
DOI: 10.1016/j.jpsychires.2022.10.023
PMID: 36270064
PMCID: PMC10540238
NLM abbreviation: J Psychiatr Res
ISSN: 0022-3956
eISSN: 1879-1379
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100000025, name: National Institute of Mental Health, award: R01 MH119165; DOI: 10.13039/100000002, name: National Institutes of Health
Language: English
Date published: 12/2022
Academic Unit: Neurology; Psychiatry; Pathology; Iowa Neuroscience Institute; Biostatistics; Neurosurgery; Otolaryngology
Record Identifier: 9984383926802771

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