Attenuated GlycoRNA-microglial transcriptional coupling in the dorsolateral prefrontal cortex of patients with major depressive disorder: an exploratory interaction-based in-silico analysis
- 1university of electronic science and technology of china
Abstract
BackgroundGlycosylated RNAs (GlycoRNAs) participate in immune recognition and intercellular communication1, but their relationship with brain cell-type transcriptional signatures in major depressive disorder (MDD) remains unclear. We examined GlycoRNA-related transcriptional coupling with microglial and other cellular signatures in the dorsolateral prefrontal cortex (DLPFC).
MethodPostmortem DLPFC transcriptomic data from 22 controls and 26 MDD patients (GSE102556)2 were analyzed. GlycoRNA-related pathway enrichment was quantified using gene set variation analysis (GSVA)3, whereas microglial, neuronal, astrocytic, and oligodendrocytic signatures were derived using single-sample gene set enrichment analysis (ssGSEA)4-6. Pearson correlations, linear regression, and generalized estimating equations (GEE) evaluated cell-type-specific associations and diagnostic interactions. Exploratory GEE results underwent false discovery rate (FDR) correction.
ResultsNo differentially expressed genes survived FDR correction, and GlycoRNA-related and cell-type signatures did not differ significantly between groups. In controls, GlycoRNA enrichment was positively associated with the microglial signature ({beta} = 0.447, FDR-P = 0.006), with significantly weaker associations for neurons, astrocytes, and oligodendrocytes (all FDR-P < 0.05). The two-way GlycoRNA x is_microglia interaction was nominally significant ({beta} = 0.210, P = 0.048), confirming that GlycoRNA transcriptional coupling is substantially stronger for microglia than for the other three cell types combined. The microglial association was numerically attenuated in MDD ({beta} difference = -0.273, P = 0.167), but diagnostic interactions were nonsignificant.
ConclusionsGlycoRNA pathway transcriptional enrichment exhibits preferential microglial association in control DLPFC. Its possible attenuation in MDD remains.
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BibTeX
@misc{xu2026attenuated,
title = {{Attenuated GlycoRNA-microglial transcriptional coupling in the dorsolateral prefrontal cortex of patients with major depressive disorder: an exploratory interaction-based in-silico analysis}},
author = {R. Xu and Y. Zhang and M. Maes},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.12.26365369},
url = {https://www.medrxiv.org/content/10.64898/2026.10.12.26365369v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Attenuated GlycoRNA-microglial transcriptional coupling in the dorsolateral prefrontal cortex of patients with major depressive disorder: an exploratory interaction-based in-silico analysis
AU - R. Xu
AU - Y. Zhang
AU - M. Maes
PY - 2026
DA - 2026/10/12
PB - medRxiv
DO - 10.64898/2026.10.12.26365369
UR - https://www.medrxiv.org/content/10.64898/2026.10.12.26365369v1
AB - BackgroundGlycosylated RNAs (GlycoRNAs) participate in immune recognition and intercellular communication1, but their relationship with brain cell-type transcriptional signatures in major depressive disorder (MDD) remains unclear. We examined GlycoRNA-related transcriptional coupling with microglial and other cellular signatures in the dorsolateral prefrontal cortex (DLPFC). MethodPostmortem DLPFC transcriptomic data from 22 controls and 26 MDD patients (GSE102556)2 were analyzed. GlycoRNA-related pathway enrichment was quantified using gene set variation analysis (GSVA)3, whereas microglial, neuronal, astrocytic, and oligodendrocytic signatures were derived using single-sample gene set enrichment analysis (ssGSEA)4-6. Pearson correlations, linear regression, and generalized estimating equations (GEE) evaluated cell-type-specific associations and diagnostic interactions. Exploratory GEE results underwent false discovery rate (FDR) correction. ResultsNo differentially expressed genes survived FDR correction, and GlycoRNA-related and cell-type signatures did not differ significantly between groups. In controls, GlycoRNA enrichment was positively associated with the microglial signature ({beta} = 0.447, FDR-P = 0.006), with significantly weaker associations for neurons, astrocytes, and oligodendrocytes (all FDR-P < 0.05). The two-way GlycoRNA x is_microglia interaction was nominally significant ({beta} = 0.210, P = 0.048), confirming that GlycoRNA transcriptional coupling is substantially stronger for microglia than for the other three cell types combined. The microglial association was numerically attenuated in MDD ({beta} difference = -0.273, P = 0.167), but diagnostic interactions were nonsignificant. ConclusionsGlycoRNA pathway transcriptional enrichment exhibits preferential microglial association in control DLPFC. Its possible attenuation in MDD remains.
ER -