Accession Number : AD1045484


Title :   Whole-Genome DNA Methylation Status Associated with Clinical PTSD Measures of OIF/OEF Veterans (Open Access)


Descriptive Note : Journal Article - Open Access


Corporate Author : U.S Army Center for Environmental Health Research Fort Detrick United States


Personal Author(s) : Hammamieh,Rasha ; Chakraborty,Nabarun ; Gautam,Aarti ; Muhie,Seid ; Yang,Routing ; Donohue,Duncan ; Daigle,B Jr J ; Kumar,Raina ; Zhang,Y ; Amara,D A ; Miller,Stacy-Ann ; Srinivasan,Seshamalini ; Flory,Janine ; Yehuda,Rachel ; Petzold,L ; Wolkowitz,O H ; Mellon,S H ; Hood,L ; Doyle,F III J ; Marmar,C ; Jett,Marti ; Jett,Marti ; Jett,Marti


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1045484.pdf


Report Date : 11 Jul 2017


Pagination or Media Count : 8


Abstract : Emerging knowledge suggests that post-traumatic stress disorder (PTSD) pathophysiology is linked to the patients' epigenetic changes, but comprehensive studies examining genome-wide methylation have not been performed. In this study, we examined genome-wide DNA methylation in peripheral whole blood in combat veterans with and without PTSD to ascertain differentially methylated probes. Discovery was initially made in a training sample comprising 48 male Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans with PTSD and 51 age/ethnicity/gender-matched combat-exposed PTSD-negative controls. Agilent whole-genome array detected 5600 differentially methylatedCpG islands (CpGI) annotated to 2800 differently methylated genes (DMGs) . The majority (84.5%) of these CpGis were hypermethylated in the PTSD cases. Functional analysis was performed using the DMGs encoding the promoter-bound CpGis to identify networks related to PTSD. The identified networks were further validated by an independent test set comprising 31 PTSD+/29 PTSD - veterans. Targeted bisulfite sequencing was also used to confirm the methylation status of 20 DMGs shown to be highly perturbed in the training set. To improve the statistical power and mitigate the assay bias and batch effects, a union set combining both training and test set was assayed using a different platform from Illumina. The pathways curated from this analysis confirmed 65% of the pool of pathways mined from training and test sets. The results highlight the importance of assay methodology and use of independent samples for discovery and validation of differentially methylated genes mined from whole blood. Nonetheless, the current study demonstrates that several important epigenetically altered networks may distinguish combat-exposed veterans with and without PTSD.


Descriptors :   DNA , genome , METHYLATION , traumatic stress disorder , military operations , veterans(military personnel) , combat operations , PATHOPHYSIOLOGY , genes , therapeutics


Subject Categories : Medicine and Medical Research
      Psychology
      Biochemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE