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Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans.

Publication ,  Journal Article
Ashley-Koch, AE; Garrett, ME; Gibson, J; Liu, Y; Dennis, MF; Kimbrel, NA; Beckham, JC; Hauser, MA ...
Published in: J Affect Disord
September 15, 2015

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)). LIMITATIONS: 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.

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Published In

J Affect Disord

DOI

EISSN

1573-2517

Publication Date

September 15, 2015

Volume

184

Start / End Page

225 / 234

Location

Netherlands

Related Subject Headings

  • White People
  • Veterans
  • United States
  • Stress Disorders, Post-Traumatic
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Male
  • Iraq War, 2003-2011
  • Humans
  • Genotype
 

Citation

APA
Chicago
ICMJE
MLA
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Ashley-Koch, A. E., Garrett, M. E., Gibson, J., Liu, Y., Dennis, M. F., Kimbrel, N. A., … Hauser, M. A. (2015). Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans. J Affect Disord, 184, 225–234. https://doi.org/10.1016/j.jad.2015.03.049
Ashley-Koch, Allison E., Melanie E. Garrett, Jason Gibson, Yutao Liu, Michelle F. Dennis, Nathan A. Kimbrel, Nathan A. Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup, Jean C. Beckham, and Michael A. Hauser. “Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans.J Affect Disord 184 (September 15, 2015): 225–34. https://doi.org/10.1016/j.jad.2015.03.049.
Ashley-Koch AE, Garrett ME, Gibson J, Liu Y, Dennis MF, Kimbrel NA, et al. Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans. J Affect Disord. 2015 Sep 15;184:225–34.
Ashley-Koch, Allison E., et al. “Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans.J Affect Disord, vol. 184, Sept. 2015, pp. 225–34. Pubmed, doi:10.1016/j.jad.2015.03.049.
Ashley-Koch AE, Garrett ME, Gibson J, Liu Y, Dennis MF, Kimbrel NA, Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup, Beckham JC, Hauser MA. Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans. J Affect Disord. 2015 Sep 15;184:225–234.
Journal cover image

Published In

J Affect Disord

DOI

EISSN

1573-2517

Publication Date

September 15, 2015

Volume

184

Start / End Page

225 / 234

Location

Netherlands

Related Subject Headings

  • White People
  • Veterans
  • United States
  • Stress Disorders, Post-Traumatic
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Male
  • Iraq War, 2003-2011
  • Humans
  • Genotype