TY - JOUR
T1 - Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans
AU - Department of Veterans Affairs Cooperative Studies Program (#575B) and Million Veteran Program
AU - Gelernter, Joel
AU - Sun, Ning
AU - Polimanti, Renato
AU - Pietrzak, Robert
AU - Levey, Daniel F.
AU - Bryois, Julien
AU - Lu, Qiongshi
AU - Hu, Yiming
AU - Li, Boyang
AU - Radhakrishnan, Krishnan
AU - Aslan, Mihaela
AU - Cheung, Kei Hoi
AU - Li, Yuli
AU - Rajeevan, Nallakkandi
AU - Sayward, Frederick
AU - Harrington, Kelly
AU - Chen, Quan
AU - Cho, Kelly
AU - Pyarajan, Saiju
AU - Sullivan, Patrick F.
AU - Quaden, Rachel
AU - Shi, Yunling
AU - Hunter-Zinck, Haley
AU - Gaziano, J. Michael
AU - Concato, John
AU - Zhao, Hongyu
AU - Stein, Murray B.
N1 - Funding Information:
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.
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85069832192&partnerID=8YFLogxK
U2 - 10.1038/s41593-019-0447-7
DO - 10.1038/s41593-019-0447-7
M3 - Article
C2 - 31358989
AN - SCOPUS:85069832192
SN - 1097-6256
VL - 22
SP - 1394
EP - 1401
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 9
ER -