Post-traumatic stress disorder (PTSD) is a major problem among military veterans and civilians alike, yet its pathophysiology remains poorly understood. We performed a genome-wide association study and bioinformatic analyses, which included 146,660 European Americans and 19,983 African Americans in the US Million Veteran Program, to identify genetic risk factors relevant to intrusive reexperiencing of trauma, which is the most characteristic symptom cluster of PTSD. In European Americans, eight distinct significant regions were identified. Three regions had values of P < 5 × 10−10: CAMKV; chromosome 17 closest to KANSL1, but within a large high linkage disequilibrium region that also includes CRHR1; and TCF4. Associations were enriched with respect to the transcriptomic profiles of striatal medium spiny neurons. No significant associations were observed in the African American cohort of the sample. Results in European Americans were replicated in the UK Biobank data. These results provide new insights into the biology of PTSD in a well-powered genome-wide association study.
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The GWAS summary statistics generated during and/or analyzed during the current study are available via dbGAP; the dbGaP accession assigned to the Million Veteran Program is phs001672.v1.p. The website is: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001672.v1.p1. Additionally, the data that support the findings of this study are available from the corresponding authors upon reasonable request.
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This research is based on data from the Million Veteran Program (MVP), Office of Research and Development, Veterans Health Administration, and was supported by the MVP and the VA Cooperative Studies Program (CSP) study no. 575B. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.
J.G. is named as a co-inventor on PCT patent application no. 15/878,640 entitled: “Genotype-guided dosing of opioid agonists,” filed 24 January 2018. M.B.S. has in the past 3 years been a consultant for Actelion, Aptinyx, Bionomics, Dart Neuroscience, Healthcare Management Technologies, Janssen, Jazz Pharmaceuticals, Neurocrine Biosciences, Oxeia Biopharmaceuticals, Pfizer, and Resilience Therapeutics. M.B.S. owns founders shares and stock options in Resilience Therapeutics and has stock options in Oxeia Biopharmaceuticals.
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Top 10,000 variants in EAs (LD pruned)
Top 10,000 variants in AAs (LD pruned)
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Gelernter, J., Sun, N., Polimanti, R. et al. Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans. Nat Neurosci 22, 1394–1401 (2019). https://doi.org/10.1038/s41593-019-0447-7
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