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Meta-Analysis
. 2015 Sep 15:184:225-34.
doi: 10.1016/j.jad.2015.03.049. Epub 2015 Jun 12.

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

Allison E Ashley-Koch  1 , Melanie E Garrett  2 , Jason Gibson  2 , Yutao Liu  2 , Michelle F Dennis  3 , Nathan A Kimbrel  3 ; Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup; Jean C Beckham  3 , Michael A Hauser  2
Collaborators, Affiliations
Meta-Analysis

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

Allison E Ashley-Koch et al. J Affect Disord. .

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.

Keywords: Combat exposure; Gene*environment interaction; Genome-wide association study; Meta-analysis; Posttraumatic stress disorder.

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Figures

Figure 1
Figure 1. Manhattan plot of the genome-wide association results in the non-Hispanic black subset
Genes which contained SNPs with p-values less than 10−5 are labeled on the plot.
Figure 2
Figure 2. Manhattan plot of the genome-wide association results in the non-Hispanic white subset
Genes which contained SNPs with p-values less than 10−5 are labeled on the plot.
Figure 3
Figure 3. Manhattan plot of the genome-wide association results in the meta-analysis of the non-Hispanic black and non-Hispanci white subsets
Genes which contained SNPs with p-values less than 10−5 are labeled on the plot.
See this image and copyright information in PMC

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