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

Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Competing Interests: Declaration of competing interest Gen Shinozaki has pending patents “Epigenetic Biomarker of Delirium Risk” in the PCT Application No. PCT/US19/51276, and in U.S. Provisional Patent No. 62/731,599. All other authors have declared that no conflict of interest exists.
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