title: An analysis of gene expression in PTSD implicates genes involved in the glucocorticoid receptor pathway and neural responses to stress.
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 amygdala 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.
authors: Research Service, VA Boston Healthcare System, Boston, MA, United States; Biomedical Genetics, Boston University School of Medicine, Boston, MA, United States; Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States. Electronic address: mark.logue@va.gov.
authors: Mark W
authors: MW
authors: Logue
authors: Department of Psychiatry & Behavioral Sciences Emory University School of Medicine, Atlanta, GA, United States.
authors: Alicia K
authors: AK
authors: Smith
authors: Biomedical Genetics, Boston University School of Medicine, Boston, MA, United States.
authors: Clinton
authors: C
authors: Baldwin
authors: National Center for PTSD, VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States.
authors: Erika J
authors: EJ
authors: Wolf
authors: Department of Psychiatry, Division of Child and Adolescent Psychiatry, Columbia University/NYSPI, New York, NY, United States.
authors: Guia
authors: G
authors: Guffanti
authors: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States.
authors: Andrew
authors: A
authors: Ratanatharathorn
authors: Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Little Rock, AR, United States.
authors: Annjanette
authors: A
authors: Stone
authors: Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Little Rock, AR, United States.
authors: Steven A
authors: SA
authors: Schichman
authors: Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA, United States.
authors: Donald
authors: D
authors: Humphries
authors: Department of Psychiatry & Behavioral Sciences Emory University School of Medicine, Atlanta, GA, United States; Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
authors: Elisabeth B
authors: EB
authors: Binder
authors: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
authors: Janine
authors: J
authors: Arloth
authors: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
authors: Andreas
authors: A
authors: Menke
authors: Institute for Genomic Biology, University of Illinois-Urbana, Champaign, IL, United States; Department of Psychology, University of Illinois-Urbana, Champaign, IL, United States.
authors: Monica
authors: M
authors: Uddin
authors: Institute for Genomic Biology, University of Illinois-Urbana, Champaign, IL, United States; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States.
authors: Derek
authors: D
authors: Wildman
authors: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States.
authors: Sandro
authors: S
authors: Galea
authors: Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States.
authors: Allison E
authors: AE
authors: Aiello
authors: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States.
authors: Karestan C
authors: KC
authors: Koenen
authors: National Center for PTSD, VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States.
authors: Mark W
authors: MW
authors: Miller
mesh_terms: D000328:Adult; D000679:Amygdala / Q000502:physiology; D001921:Brain / Q000502:physiology; D016022:Case-Control Studies; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011965:Receptors, Glucocorticoid / Q000097:blood* / Q000235:genetics*; D013313:Stress Disorders, Post-Traumatic / Q000097:blood* / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics; D059467:Transcriptome; D014481:United States; D014728:Veterans
chemical_list: D011965:Receptors, Glucocorticoid
keywords: ATP6AP1L; DSCAM; Gene expression; Glucocorticoid responsive; PTSD; Whole blood