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PTSD; Gene expression; Whole blood; DSCAM; ATP6AP1L; Glucocorticoid responsive
Abstract:
We examined the association between posttraumatic stress disorder (PTSD)
and gene expression using whole blood samples from a cohort of
trauma-exposed white non-Hispanic male veterans (115 cases and 28
controls). 10,264 probes of genes and gene transcripts were analyzed. We
found 41 that were differentially expressed in PTSD cases versus
controls (multiple-testing corrected p <0.05). The most significant was
DSCAM, a neurological gene expressed widely in the developing brain and
in the annygdala and hippocampus of the adult brain. We then examined
the 41 differentially expressed genes in a meta-analysis using two
replication cohorts and found significant associations with PTSD for 7
of the 41 (p <0.05), one of which (ATP6AP1L) survived multiple-testing
correction. There was also broad evidence of overlap across the
discovery and replication samples for the entire set of genes implicated
in the discovery data based on the direction of effect and an enrichment
of p <0.05 significant probes beyond what would be expected under the
null. Finally, we found that the set of differentially expressed genes
from the discovery sample was enriched for genes responsive to
glucocorticoid signaling with most showing reduced expression in PTSD
cases compared to controls. Published by Elsevier Ltd.
