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Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden

Published online by Cambridge University Press:  29 November 2022

Brandon Nichter ,
Dora Koller ,
Flavio De Angelis ,
Jiawei Wang ,
Matthew J. Girgenti ,
Peter J. Na ,
Melanie L. Hill ,
Sonya B. Norman ,
John H. Krystal  and
Joel Gelernter
...Show all authors
Brandon Nichter*
Affiliation:
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
Dora Koller
Affiliation:
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA VA Connecticut Healthcare System, West Haven, CT, USA,
Flavio De Angelis
Affiliation:
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
Jiawei Wang
Affiliation:
Computational Biology & Bioinformatics, Yale University, New Haven, CT, USA
Matthew J. Girgenti
Affiliation:
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA
Peter J. Na
Affiliation:
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA
Melanie L. Hill
Affiliation:
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA VA San Diego Healthcare System, San Diego, CA, USA
Sonya B. Norman
Affiliation:
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA VA San Diego Healthcare System, San Diego, CA, USA National Center for PTSD, White River Junction, VT, USA
John H. Krystal
Affiliation:
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA
Joel Gelernter
Affiliation:
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA
Renato Polimanti
Affiliation:
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA VA Connecticut Healthcare System, West Haven, CT, USA,
Robert H. Pietrzak
Affiliation:
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA Department of Social and Behavioral Sciences, Yale School of Public Health, New Haven, CT, USA
*
Author for correspondence: Brandon Nichter, E-mail: brandon.nichter@yale.edu
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Abstract

Background

Little is known about environmental factors that may influence associations between genetic liability to suicidality and suicidal behavior.

Methods

This study examined whether a suicidality polygenic risk score (PRS) derived from a large genome-wide association study (N = 122,935) was associated with suicide attempts in a population-based sample of European-American US military veterans (N = 1664; 92.5% male), and whether cumulative lifetime trauma exposure moderated this association.

Results

Eighty-five veterans (weighted 6.3%) reported a history of suicide attempt. After adjusting for sociodemographic and psychiatric characteristics, suicidality PRS was associated with lifetime suicide attempt (odds ratio 2.65; 95% CI 1.37–5.11). A significant suicidality PRS-by-trauma exposure interaction emerged, such that veterans with higher levels of suicidality PRS and greater trauma burden had the highest probability of lifetime suicide attempt (16.6%), whereas the probability of attempts was substantially lower among those with high suicidality PRS and low trauma exposure (1.4%). The PRS-by-trauma interaction effect was enriched for genes implicated in cellular and developmental processes, and nervous system development, with variants annotated to the DAB2 and SPNS2 genes, which are implicated in inflammatory processes. Drug repurposing analyses revealed upregulation of suicide gene-sets in the context of medrysone, a drug targeting chronic inflammation, and clofibrate, a triacylglyceride level lowering agent.

Conclusion

Results suggest that genetic liability to suicidality is associated with increased risk of suicide attempt among veterans, particularly in the presence of high levels of cumulative trauma exposure. Additional research is warranted to investigate whether incorporation of genomic information may improve suicide prediction models.

Keywords

Geneticsinflammationmilitarypolygenic risksuicide attempttraumaveterans
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 13 , October 2023 , pp. 6325 - 6333
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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