TY - JOUR
T1 - Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans
AU - Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup
AU - Ashley-Koch, Allison E.
AU - Garrett, Melanie E.
AU - Gibson, Jason
AU - Liu, Yutao
AU - Dennis, Michelle F.
AU - Kimbrel, Nathan A.
AU - Beckham, Jean C.
AU - Hauser, Michael A.
N1 - Funding Information:
This work was supported by the Department of Veterans Affairs’ (VA) Mid-Atlantic Mental Illness Research, Education, and Clinical Center (MIRECC) and the Research & Development and Mental Health Services of the Durham Veterans Affairs Medical Center . Dr. Kimbrel was supported by a Career Development Award ( IK2 CX000525 ) from the Clinical Science Research and Development ( CSR&D ) Service of the VA Office of Research and Development. Dr. Beckham was supported by a Research Career Scientist Award from VA CSR&D . While VA CSR&D supported this work through its support of Drs. Kimbrel and Beckham, it played no role in study design, data collection, data analysis, manuscript preparation, or the decision to submit this article for publication. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the VA or the United States government. No conflicts of interest exist.
Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/6/25
Y1 - 2015/6/25
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.
KW - Combat exposure
KW - Gene
KW - Genome-wide association study
KW - Meta-analysis
KW - Posttraumatic stress disorder
KW - environment interaction
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U2 - 10.1016/j.jad.2015.03.049
DO - 10.1016/j.jad.2015.03.049
M3 - Article
C2 - 26114229
AN - SCOPUS:84934984598
SN - 0165-0327
VL - 184
SP - 225
EP - 234
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
M1 - 7362
ER -