title: Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans.
abstract: BACKGROUND
  Posttraumatic stress disorder (PTSD) is a psychiatric disorder that can develop after experiencing traumatic events. A genome-wide association study (GWAS) design was used to identify genetic risk factors for PTSD within a multi-racial sample primarily composed of U.S. veterans.
  
  
  METHODS
  Participants were recruited at multiple medical centers, and structured interviews were used to establish diagnoses. Genotypes were generated using three Illumina platforms and imputed with global reference data to create a common set of SNPs. SNPs that increased risk for PTSD were identified with logistic regression, while controlling for gender, trauma severity, and population substructure. Analyses were run separately in non-Hispanic black (NHB; n = 949) and non-Hispanic white (NHW; n = 759) participants. Meta-analysis was used to combine results from the two subsets.
  
  
  RESULTS
  SNPs within several interesting candidate genes were nominally significant. Within the NHB subset, the most significant genes were UNC13C and DSCAM. Within the NHW subset, the most significant genes were TBC1D2, SDC2 and PCDH7. In addition, PRKG1 and DDX60L were identified through meta-analysis. The top genes for the three analyses have been previously implicated in neurologic processes consistent with a role in PTSD. Pathway analysis of the top genes identified alternative splicing as the top GO term in all three analyses (FDR q < 3.5 × 10(-5)).
  
  
  CONCLUSIONS
  No individual SNPs met genome-wide significance in the analyses.
  
  
  CONCLUSIONS
  This multi-racial PTSD GWAS identified biologically plausible candidate genes and suggests that post-transcriptional regulation may be important to the pathology of PTSD; however, replication of these findings is needed.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, United States. Electronic address: allison.ashleykoch@duke.edu.
authors.forename: Allison E
authors.initials: AE
authors.lastname: Ashley-Koch
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, United States.
authors.forename: Melanie E
authors.initials: ME
authors.lastname: Garrett
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, United States.
authors.forename: Jason
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, United States.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Durham Veterans Affairs Medical Center, Durham, NC, United States; The VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center, Durham, NC, United States; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States.
authors.forename: Michelle F
authors.initials: MF
authors.lastname: Dennis
authors.affiliation: Durham Veterans Affairs Medical Center, Durham, NC, United States; The VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center, Durham, NC, United States; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Kimbrel
authors.affiliation: Durham Veterans Affairs Medical Center, Durham, NC, United States; The VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center, Durham, NC, United States; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Beckham
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
mesh_terms: D000328:Adult; D055826:Afghan Campaign 2001-; D001741:Black or African American / Q000235:genetics; D017398:Alternative Splicing / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D054542:Iraq War, 2003-2011; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics*; D014481:United States; D014728:Veterans / Q000523:psychology*; D044465:White People / Q000235:genetics
keywords: Combat exposure; Gene*environment interaction; Genome-wide association study; Meta-analysis; Posttraumatic stress disorder