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Polygenic prediction of PTSD trajectories in 9/11 responders

Published online by Cambridge University Press:  23 October 2020

Monika A. Waszczuk
Affiliation:
Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA
Anna R. Docherty
Affiliation:
Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
Andrey A. Shabalin
Affiliation:
Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA
Jiaju Miao
Affiliation:
Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA
Xiaohua Yang
Affiliation:
World Trade Center Health and Wellness Program, Department of Medicine, Stony Brook University, Stony Brook, NY, USA
Pei-Fen Kuan
Affiliation:
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA
Evelyn Bromet
Affiliation:
Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA
Roman Kotov
Affiliation:
Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA
Benjamin J. Luft
Affiliation:
World Trade Center Health and Wellness Program, Department of Medicine, Stony Brook University, Stony Brook, NY, USA
Corresponding

Abstract

Background

Genetics hold promise of predicting long-term post-traumatic stress disorder (PTSD) outcomes following trauma. The aim of the current study was to test whether six hypothesized polygenic risk scores (PRSs) developed to capture genetic vulnerability to psychiatric conditions prospectively predict PTSD onset, severity, and 18-year course after trauma exposure.

Methods

Participants were 1490 responders to the World Trade Center (WTC) disaster (mean age at 9/11 = 38.81 years, s.d. = 8.20; 93.5% male; 23.8% lifetime WTC-related PTSD diagnosis). Prospective longitudinal data on WTC-related PTSD symptoms were obtained from electronic medical records and modelled as PTSD trajectories using growth mixture model analysis. Independent regression models tested whether six hypothesized psychiatric PRSs (PTSD-PRS, Re-experiencing-PRS, Generalized Anxiety-PRS, Schizophrenia-PRS, Depression-PRS, and Neuroticism-PRS) are predictive of WTC-PTSD outcomes: lifetime diagnoses, average symptom severity, and 18-year symptom trajectory. All analyses were adjusted for population stratification, 9/11 exposure severity, and multiple testing.

Results

Depression-PRS predicted PTSD diagnostic status (OR 1.37, CI 1.17–1.61, adjusted p = 0.001). All PRSs, except PTSD-PRS, significantly predicted average PTSD symptoms (β = 0.06–0.10, adjusted p < 0.05). Re-experiencing-PRS, Generalized Anxiety-PRS and Schizophrenia-PRS predicted the high severity PTSD trajectory class (ORs 1.21–1.28, adjusted p < 0.05). Finally, PRSs prediction was independent of 9/11 exposure severity and jointly accounted for 3.7 times more variance in PTSD symptoms than the exposure severity.

Conclusions

Psychiatric PRSs prospectively predicted WTC-related PTSD lifetime diagnosis, average symptom severity, and 18-year trajectory in responders to 9/11 disaster. Jointly, PRSs were more predictive of subsequent PTSD than the exposure severity. In the future, PRSs may help identify at-risk responders who might benefit from targeted prevention approaches.

Type
Original Articles
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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Footnotes

*

Denotes joint Senior Authors.

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Polygenic prediction of PTSD trajectories in 9/11 responders
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