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

Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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). 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.

Original languageEnglish (US)
Article number7362
Pages (from-to)225-234
Number of pages10
JournalJournal of Affective Disorders
Volume184
DOIs
StatePublished - Jun 25 2015

Fingerprint

Afghanistan
Iraq
Genome-Wide Association Study
Veterans
Post-Traumatic Stress Disorders
Single Nucleotide Polymorphism
Genes
Meta-Analysis
Alternative Splicing
Nervous System
Psychiatry
Logistic Models
Genotype
Genome
Interviews
Pathology
Wounds and Injuries
Population

Keywords

  • Combat exposure
  • Gene
  • Genome-wide association study
  • Meta-analysis
  • Posttraumatic stress disorder
  • environment interaction

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup (2015). Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans. Journal of Affective Disorders, 184, 225-234. [7362]. https://doi.org/10.1016/j.jad.2015.03.049

Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans. / Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup.

In: Journal of Affective Disorders, Vol. 184, 7362, 25.06.2015, p. 225-234.

Research output: Contribution to journalArticle

Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup 2015, 'Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans', Journal of Affective Disorders, vol. 184, 7362, pp. 225-234. https://doi.org/10.1016/j.jad.2015.03.049
Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup. Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans. Journal of Affective Disorders. 2015 Jun 25;184:225-234. 7362. https://doi.org/10.1016/j.jad.2015.03.049
Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup. / Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans. In: Journal of Affective Disorders. 2015 ; Vol. 184. pp. 225-234.
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abstract = "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). 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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AU - Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup

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AU - Garrett, Melanie E.

AU - Gibson, Jason

AU - Liu, Yutao

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N2 - 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). 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.

AB - 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). 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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