Post-traumatic stress following military deployment: Genetic associations and cross-disorder genetic correlations

Yunpeng Wang; Karen-Inge Karstoft; Caroline M Nievergelt; Adam X Maihofer; Murray B Stein; Robert J Ursano; Jonas Bybjerg-Grauholm; Marie Bækvad-Hansen; David M Hougaard; Ole A Andreassen; Thomas Werge; Wesley K Thompson; Søren B Andersen

doi:10.1016/j.jad.2019.04.070

Post-traumatic stress following military deployment: Genetic associations and cross-disorder genetic correlations

Yunpeng Wang, Karen-Inge Karstoft, Caroline M Nievergelt, Adam X Maihofer, Murray B Stein, Robert J Ursano, Jonas Bybjerg-Grauholm, Marie Bækvad-Hansen, David M Hougaard, Ole A Andreassen, Thomas Werge, Wesley K Thompson, Søren B Andersen

Department of Clinical Medicine

1 Citation (Scopus)

Abstract

BACKGROUND: Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder that occurs with relatively high frequency after deployment to warzones (∼10%). While twin studies have estimated the heritability to be up to 40%, thus indicating a considerable genetic component in the etiology, the biological mechanisms underlying risk and development of PTSD remain unknown.

METHODS: Here, we conduct a genome-wide association study (GWAS; N = 2,481) to identify genome regions that associate with PTSD in a highly homogenous, trauma-exposed sample of Danish soldiers deployed to war and conflict zones. We perform integrated analyses of our results with gene-expression and chromatin-contact datasets to prioritized genes. We also leverage on other large GWAS (N>300,000) to investigate genetic correlations between PTSD and other psychiatric disorders and traits.

RESULTS: We discover, but do not replicate, one region, 4q31, close to the IL15 gene, which is genome-wide significantly associated with PTSD. We demonstrate that gene-set enrichment, polygenic risk score and genetic correlation analyses show consistent and significant genetic correlations between PTSD and depression, insomnia and schizophrenia.

LIMITATIONS: The limited sample size, the lack of replication, and the PTSD case definition by questionnaire are limitations to the study.

CONCLUSIONS: Our results suggest that genetic perturbations of inflammatory response may contribute to the risk of PTSD. In addition, shared genetic components contribute to observed correlations between PTSD and depression, insomnia and schizophrenia.

Original language	English
Journal	Journal of Affective Disorders
Volume	252
Pages (from-to)	350-357
Number of pages	8
ISSN	0165-0327
DOIs	https://doi.org/10.1016/j.jad.2019.04.070
Publication status	Published - 1 Jun 2019

Keywords

Faculty of Social Sciences
IL15
PTSD
Cross-disorder genetic correlations
Inflammation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jad.2019.04.070

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Wang, Y., Karstoft, K-I., Nievergelt, C. M., Maihofer, A. X., Stein, M. B., Ursano, R. J., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Hougaard, D. M., Andreassen, O. A., Werge, T., Thompson, W. K., & Andersen, S. B. (2019). Post-traumatic stress following military deployment: Genetic associations and cross-disorder genetic correlations. Journal of Affective Disorders, 252, 350-357. https://doi.org/10.1016/j.jad.2019.04.070

Wang, Y, Karstoft, K-I, Nievergelt, CM, Maihofer, AX, Stein, MB, Ursano, RJ, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Hougaard, DM, Andreassen, OA, Werge, T, Thompson, WK & Andersen, SB 2019, 'Post-traumatic stress following military deployment: Genetic associations and cross-disorder genetic correlations', Journal of Affective Disorders, vol. 252, pp. 350-357. https://doi.org/10.1016/j.jad.2019.04.070

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title = "Post-traumatic stress following military deployment: Genetic associations and cross-disorder genetic correlations",

abstract = "BACKGROUND: Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder that occurs with relatively high frequency after deployment to warzones (∼10%). While twin studies have estimated the heritability to be up to 40%, thus indicating a considerable genetic component in the etiology, the biological mechanisms underlying risk and development of PTSD remain unknown.METHODS: Here, we conduct a genome-wide association study (GWAS; N = 2,481) to identify genome regions that associate with PTSD in a highly homogenous, trauma-exposed sample of Danish soldiers deployed to war and conflict zones. We perform integrated analyses of our results with gene-expression and chromatin-contact datasets to prioritized genes. We also leverage on other large GWAS (N>300,000) to investigate genetic correlations between PTSD and other psychiatric disorders and traits.RESULTS: We discover, but do not replicate, one region, 4q31, close to the IL15 gene, which is genome-wide significantly associated with PTSD. We demonstrate that gene-set enrichment, polygenic risk score and genetic correlation analyses show consistent and significant genetic correlations between PTSD and depression, insomnia and schizophrenia.LIMITATIONS: The limited sample size, the lack of replication, and the PTSD case definition by questionnaire are limitations to the study.CONCLUSIONS: Our results suggest that genetic perturbations of inflammatory response may contribute to the risk of PTSD. In addition, shared genetic components contribute to observed correlations between PTSD and depression, insomnia and schizophrenia.",

keywords = "Faculty of Social Sciences, IL15, PTSD, Cross-disorder genetic correlations, Inflammation",

author = "Yunpeng Wang and Karen-Inge Karstoft and Nievergelt, {Caroline M} and Maihofer, {Adam X} and Stein, {Murray B} and Ursano, {Robert J} and Jonas Bybjerg-Grauholm and Marie B{\ae}kvad-Hansen and Hougaard, {David M} and Andreassen, {Ole A} and Thomas Werge and Thompson, {Wesley K} and Andersen, {S{\o}ren B}",

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month = jun,

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doi = "10.1016/j.jad.2019.04.070",

language = "English",

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pages = "350--357",

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T1 - Post-traumatic stress following military deployment

T2 - Genetic associations and cross-disorder genetic correlations

AU - Wang, Yunpeng

AU - Karstoft, Karen-Inge

AU - Nievergelt, Caroline M

AU - Maihofer, Adam X

AU - Stein, Murray B

AU - Ursano, Robert J

AU - Bybjerg-Grauholm, Jonas

AU - Bækvad-Hansen, Marie

AU - Hougaard, David M

AU - Andreassen, Ole A

AU - Werge, Thomas

AU - Thompson, Wesley K

AU - Andersen, Søren B

PY - 2019/6/1

Y1 - 2019/6/1

N2 - BACKGROUND: Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder that occurs with relatively high frequency after deployment to warzones (∼10%). While twin studies have estimated the heritability to be up to 40%, thus indicating a considerable genetic component in the etiology, the biological mechanisms underlying risk and development of PTSD remain unknown.METHODS: Here, we conduct a genome-wide association study (GWAS; N = 2,481) to identify genome regions that associate with PTSD in a highly homogenous, trauma-exposed sample of Danish soldiers deployed to war and conflict zones. We perform integrated analyses of our results with gene-expression and chromatin-contact datasets to prioritized genes. We also leverage on other large GWAS (N>300,000) to investigate genetic correlations between PTSD and other psychiatric disorders and traits.RESULTS: We discover, but do not replicate, one region, 4q31, close to the IL15 gene, which is genome-wide significantly associated with PTSD. We demonstrate that gene-set enrichment, polygenic risk score and genetic correlation analyses show consistent and significant genetic correlations between PTSD and depression, insomnia and schizophrenia.LIMITATIONS: The limited sample size, the lack of replication, and the PTSD case definition by questionnaire are limitations to the study.CONCLUSIONS: Our results suggest that genetic perturbations of inflammatory response may contribute to the risk of PTSD. In addition, shared genetic components contribute to observed correlations between PTSD and depression, insomnia and schizophrenia.

AB - BACKGROUND: Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder that occurs with relatively high frequency after deployment to warzones (∼10%). While twin studies have estimated the heritability to be up to 40%, thus indicating a considerable genetic component in the etiology, the biological mechanisms underlying risk and development of PTSD remain unknown.METHODS: Here, we conduct a genome-wide association study (GWAS; N = 2,481) to identify genome regions that associate with PTSD in a highly homogenous, trauma-exposed sample of Danish soldiers deployed to war and conflict zones. We perform integrated analyses of our results with gene-expression and chromatin-contact datasets to prioritized genes. We also leverage on other large GWAS (N>300,000) to investigate genetic correlations between PTSD and other psychiatric disorders and traits.RESULTS: We discover, but do not replicate, one region, 4q31, close to the IL15 gene, which is genome-wide significantly associated with PTSD. We demonstrate that gene-set enrichment, polygenic risk score and genetic correlation analyses show consistent and significant genetic correlations between PTSD and depression, insomnia and schizophrenia.LIMITATIONS: The limited sample size, the lack of replication, and the PTSD case definition by questionnaire are limitations to the study.CONCLUSIONS: Our results suggest that genetic perturbations of inflammatory response may contribute to the risk of PTSD. In addition, shared genetic components contribute to observed correlations between PTSD and depression, insomnia and schizophrenia.

KW - Faculty of Social Sciences

KW - IL15

KW - PTSD

KW - Cross-disorder genetic correlations

KW - Inflammation

U2 - 10.1016/j.jad.2019.04.070

DO - 10.1016/j.jad.2019.04.070

M3 - Journal article

C2 - 30999091

SN - 0165-0327

VL - 252

SP - 350

EP - 357

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

ER -

Post-traumatic stress following military deployment: Genetic associations and cross-disorder genetic correlations

Abstract

Keywords

UN SDGs

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