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.

此前，我们的研究表明，促炎细胞因子基因TNF-α中 CpG 位点的 DNA 甲基化 (DNAm) 水平随着衰老而降低，这表明 DNAm 在衰老和炎症过程中的潜在作用导致增加的风险谵妄。然而，尚未直接调查谵妄病例和非谵妄对照组之间的 DNAm 差异。因此，我们检查了谵妄患者和对照组之间血液中全基因组 DNAm 的差异，以确定有用的谵妄表观遗传生物标志物。通过全基因组 DNAm 病例对照关联研究分析了来自总共 87 名受试者（43 例谵妄病例）的数据。鉴定了LDLRAD4基因附近的全基因组显着 CpG 位点（p = 5.07E-8）。此外，过度代表性分析显示了几个重要的途径，错误发现率调整后的p值 < 0.05。基因本体论术语的顶级通路是免疫反应，京都基因和基因组百科全书术语的第二个顶级通路是胆碱能突触。谵妄和非谵妄对照患者在基因和通路水平上均显示出与免疫/炎症反应相关的显着 DNAm 差异。这一发现表明血液中的 DNAm 状态有可能用作谵妄的表观遗传生物标志物。