Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans

• Published in: Nature neuroscience Vol. 22; no. 9; pp. 1394 - 1401
• Main Authors: Gelernter, Joel, Sun, Ning, Polimanti, Renato, Pietrzak, Robert, Levey, Daniel F., Bryois, Julien, Lu, Qiongshi, Hu, Yiming, Li, Boyang, Radhakrishnan, Krishnan, Aslan, Mihaela, Cheung, Kei-Hoi, Li, Yuli, Rajeevan, Nallakkandi, Sayward, Frederick, Harrington, Kelly, Chen, Quan, Cho, Kelly, Pyarajan, Saiju, Sullivan, Patrick F., Quaden, Rachel, Shi, Yunling, Hunter-Zinck, Haley, Gaziano, J. Michael, Concato, John, Zhao, Hongyu, Stein, Murray B.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2019; Nature Publishing Group
• Subjects: 45/43; 631/208/1515; 631/208/205; 631/208/212; 631/208/457; 692/699/476/1830; Adult; Animal Genetics and Genomics; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Chromosome 17; Chromosomes; Cohort Studies; Diagnosis; Female; Genetic Predisposition to Disease - genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Humans; Linkage disequilibrium; Male; Mental disorders; Military personnel; Military psychology; Minority & ethnic groups; Neostriatum; Neurobiology; Neurosciences; Post traumatic stress disorder; Psychological aspects; Psychological stress; Risk analysis; Risk factors; Spiny neurons; Stress Disorders, Post-Traumatic - genetics; Trauma; United States; Veterans; Veterans Health; United States; United States > US
• ISSN: 1097-6256; 1546-1726; 1546-1726
• DOI: 10.1038/s41593-019-0447-7

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. This study identifies eight significant genetic associations with intrusive reexperiencing of trauma in post-traumatic stress disorder (PTSD) from the Million Veteran Program (MVP), a large biobank focused on US veterans.