As potential regulators of DNA accessibility and activity, epigenetic 
modifications offer a mechanism by which the environment can moderate the 
effects of genes. To date, however, there have been relatively few studies 
assessing epigenetic modifications associated with post-traumatic stress 
disorder (PTSD). Here we investigate PTSD-associated methylation differences in 
33 genes previously shown to differ in whole blood-derived gene expression 
levels between those with vs. without the disorder. Drawing on DNA samples 
similarly obtained from whole blood in 100 individuals, 23 with and 77 without 
lifetime PTSD, we used methylation microarray data to assess whether these 33 
candidate genes showed epigenetic signatures indicative of increased risk for, 
or resilience to, PTSD. Logistic regression analyses were performed to assess 
the main and interacting effects of candidate genes' methylation values and 
number of potentially traumatic events (PTEs), adjusting for age and other 
covariates. Results revealed that only one candidate gene - MAN2C1} - showed a 
significant methylation x PTE interaction, such that those with both higher 
MAN2C1 methylation and greater exposure to PTEs showed a marked increase in risk 
of lifetime PTSD (OR 4.35, 95% CI: 1.07, 17.77, p=0.04). These results indicate 
that MAN2C1 methylation levels modify cumulative traumatic burden on risk of 
PTSD, and suggest that both gene expression and epigenetic changes at specific 
loci are associated with this disorder.