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• W4387496908 abstract "The link between posttraumatic stress disorder (PTSD) and the immune system is supported by multiple studies that identified DNA methylation (DNAm) differences in immune-related genes in PTSD, as well as changes in cell composition in those with PTSD. Thus, correcting for cell-type composition, as typically performed in blood-based epigenomic studies, may obscure some PTSD-associated signals. Recently, a blood transcriptomic study of PTSD identified immune cell type-specific differentially expressed genes. Here, we present the results of the largest cell-type specific epigenome-wide association study (EWAS) of PTSD to date. This study includes 3277 participants (1351 PTSD cases and 1926 trauma-exposed controls) from 11 cohorts participating in the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup. PTSD assessment was harmonized according to the recommendations of PGC-PTSD Workgroup. Peripheral DNAm was assayed by the MethylationEPIC BeadChip. A common QC pipeline was applied to each of the cohorts. Within each cohort, a cell-type specific EWAS was conducted using the R package TOAST. Reduced representation oxidative bisulfite-sequencing of neuronal nuclei, isolated from orbitofrontal cortex of 25 PTSD cases and 13 controls was used to examine cross-tissue associations for the epigenome-wide significant (p < 9e-8) probes from the cell-specific EWAS, with an experiment-wide correction of p < 5e-4. This cell-type specific EWAS identified 96 epigenome-wide significant CpGs associated with PTSD: 5 in Natural Killer cells, 1 in CD4+T cells, 2 in CD8+T cells, and 88 in B cells. Most were in genes involved in inflammation and oxidative stress, including CpGs in RORA (cg18730873; p = 1.13E-08) and NR3C1 (cg12466613; p = 3.79E-08) that have been previously implicated in PTSD. Importantly, 2 B cell PTSD-associated CpGs in IGFBP2 (cg05414479, p = 2.17E-04) and RAD21L1 (cg16922058, p = 3.98E-05) were associated with PTSD in postmortem neuronal nuclei with opposite direction of effect. IGFBP2 is involved in stress resilience and RAD21L1 is implicated in multiple sclerosis (MS). This multi-ethnic study is the largest cell-type specific PTSD study to date, and the first to identify EWAS-significant cell-type specific PTSD-associated methylation loci. Our findings show B-cell specific DNAm changes associated with PTSD. B cells contribute to brain neuronal processes and are involved in neuroinflammatory diseases, such as MS. B cell-specific methylation signatures may play a role in an immune-specific response in those with PTSD." @default.
• W4387496908 created "2023-10-11" @default.
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• W4387496908 date "2023-10-01" @default.
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• W4387496908 title "25. EPIGENOME-WIDE META-ANALYSIS OF > 3200 MILITARY AND CIVILIAN PARTICIPANTS IDENTIFIES CELL-TYPE SPECIFIC DNA METHYLATION SIGNALS ASSOCIATED WITH PTSD" @default.
• W4387496908 doi "https://doi.org/10.1016/j.euroneuro.2023.08.136" @default.
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