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. 2019 Mar;28(1):e1767.
doi: 10.1002/mpr.1767. Epub 2019 Feb 14.

Genomics of posttraumatic stress disorder in veterans: Methods and rationale for Veterans Affairs Cooperative Study #575B

Krishnan Radhakrishnan  1   2 , Mihaela Aslan  1   3 , Kelly M Harrington  4   5 , Robert H Pietrzak  1   6 , Grant Huang  7 , Sumitra Muralidhar  7 , Kelly Cho  4 , Rachel Quaden  4 , David Gagnon  4   8 , Saiju Pyarajan  4 , Ning Sun  1   3 , Hongyu Zhao  1   3 , Michael Gaziano  4   9 , John Concato  1   3 , Murray B Stein  10   11 , Joel Gelernter  3   12
Affiliations

Genomics of posttraumatic stress disorder in veterans: Methods and rationale for Veterans Affairs Cooperative Study #575B

Krishnan Radhakrishnan et al. Int J Methods Psychiatr Res. 2019 Mar.

Erratum in

  • ERRATUM.
    [No authors listed] [No authors listed] Int J Methods Psychiatr Res. 2019 Dec;28(4):e1783. doi: 10.1002/mpr.1783. Int J Methods Psychiatr Res. 2019. PMID: 31885152 Free PMC article. No abstract available.

Abstract

Objectives: Heritability in the risk for developing posttraumatic stress disorder (PTSD) has been established, but most genome-wide association studies (GWASs) of PTSD involve relatively small sample sizes and limited identification of associated genetic loci. This report describes the methodology of a Veterans Affairs (VA) Cooperative Studies Program GWAS of PTSD among combat-exposed U.S. veterans.

Methods: Probable cases (with PTSD) and probable controls (without PTSD) were identified from among veterans enrolled in the VA Million Veteran Program (MVP) with an algorithm developed using questionnaire responses and electronic health record information. This algorithm, based on a statistical model, relied on medical chart reviews as a reference standard and was refined using telephone interviews. Subsequently, to evaluate the impact of probabilistic phenotyping on statistical power, the threshold probability for case-control selection was varied in simulations.

Results: As of September 2018, >695,000 veterans have enrolled in MVP. For current analyses, genotyping data were available for >353,000 participants, including >83,000 combat-exposed veterans. A threshold probability of 0.7 for case and control designation yielded an interim >16,000 cases and >33,000 controls.

Conclusions: A formal methodological approach was used to identify cases and controls for subsequent GWAS analyses to identify genetic risk loci for PTSD.

Trial registration: ClinicalTrials.gov NCT02256644.

Keywords: Clinician-Administered PTSD Scale; combat-exposed veterans; genomics; medical record review; posttraumatic stress disorder (PTSD).

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Figures

Figure 1
Figure 1
Schematic of algorithm for selecting PTSD cases and controls from the VA EHR. EHR: electronic health record; ICD: International Classification of Diseases; PCL: PTSD Checklist; PTSD: posttraumatic stress disorder; VHA: Veterans Health Administration
See this image and copyright information in PMC

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