Associations of polygenic risk scores with posttraumatic stress symptom trajectories following combat deployment

Laura Campbell-Sills; Santiago Papini; Sonya B Norman; Karmel W Choi; Feng He; Xiaoying Sun; Ronald C Kessler; Robert J Ursano; Sonia Jain; Murray B Stein

doi:10.1017/S0033291723000211

Associations of polygenic risk scores with posttraumatic stress symptom trajectories following combat deployment

Psychol Med. 2023 Mar 6;53(14):1-10. doi: 10.1017/S0033291723000211. Online ahead of print.

Authors

Laura Campbell-Sills¹, Santiago Papini^{1

2}, Sonya B Norman^{1

3

4}, Karmel W Choi^{5

6

7}, Feng He⁸, Xiaoying Sun⁸, Ronald C Kessler⁹, Robert J Ursano¹⁰, Sonia Jain⁸, Murray B Stein^{1

8

11}

Affiliations

¹ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
² Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
³ Executive Division, National Center for PTSD, White River Junction, VT, USA.
⁴ VA Center of Excellence for Stress and Mental Health, San Diego, CA, USA.
⁵ Department of Psychiatry, Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
⁶ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁷ Stanley Center for Psychiatric Research, Broad Institute, Boston, MA, USA.
⁸ Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
⁹ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.
¹⁰ Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
¹¹ Psychiatry Service, VA San Diego Healthcare System, San Diego, CA, USA.

Abstract

Background: Identification of genetic risk factors may inform the prevention and treatment of posttraumatic stress disorder (PTSD). This study evaluates the associations of polygenic risk scores (PRS) with patterns of posttraumatic stress symptoms following combat deployment.

Method: US Army soldiers of European ancestry (n = 4900) provided genomic data and ratings of posttraumatic stress symptoms before and after deployment to Afghanistan in 2012. Latent growth mixture modeling was used to model posttraumatic stress symptom trajectories among participants who provided post-deployment data (n = 4353). Multinomial logistic regression models tested independent associations between trajectory membership and PRS for PTSD, major depressive disorder (MDD), schizophrenia, neuroticism, alcohol use disorder, and suicide attempt, controlling for age, sex, ancestry, and exposure to potentially traumatic events, and weighted to account for uncertainty in trajectory classification and missing data.

Results: Participants were classified into low-severity (77.2%), increasing-severity (10.5%), decreasing-severity (8.0%), and high-severity (4.3%) posttraumatic stress symptom trajectories. Standardized PTSD-PRS and MDD-PRS were associated with greater odds of membership in the high-severity v. low-severity trajectory [adjusted odds ratios and 95% confidence intervals, 1.23 (1.06-1.43) and 1.18 (1.02-1.37), respectively] and the increasing-severity v. low-severity trajectory [1.12 (1.01-1.25) and 1.16 (1.04-1.28), respectively]. Additionally, MDD-PRS was associated with greater odds of membership in the decreasing-severity v. low-severity trajectory [1.16 (1.03-1.31)]. No other associations were statistically significant.

Conclusions: Higher polygenic risk for PTSD or MDD is associated with more severe posttraumatic stress symptom trajectories following combat deployment. PRS may help stratify at-risk individuals, enabling more precise targeting of treatment and prevention programs.

Keywords: Latent growth mixture modeling; military personnel; polygenic risk scores; posttraumatic stress; trauma.

Abstract

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