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J Affect Disord. 2019 Jun 1;252:350-357. doi: 10.1016/j.jad.2019.04.070. Epub 2019 Apr 9.

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

Author information

1
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Institute of Biological Psychiatry, Mental Health Center St. Hans, Mental Health Services Copenhagen, Boserupvej 2, DK-4000 Roskilde, Denmark; Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Kirkeveien 166, 0450 Oslo, Norway; Department of Psychology, University of Oslo, Harald Schelderups Hus Forskningsveien 3A 0373 Oslo.
2
Research and Knowledge Center, The Danish Veteran Center, Garnisonen 1, 4100 Ringsted, Denmark; Department of Psychology, University of Copenhagen, Øster Farimagsgade 2A, 1353 Copenhagen, Denmark. Electronic address: vetc-vic01@mil.dk.
3
VA Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla Village Drive 3350, 92161 La Jolla, CA, USA; Department of Psychiatry, School of Medicine, University of California San Diego, Gilman Drive 9500, 92093 La Jolla, CA, USA.
4
Department of Psychiatry, School of Medicine, University of California San Diego, Gilman Drive 9500, 92093 La Jolla, CA, USA; Department of Family Medicine and Public Health, University of California San Diego, Gilman Drive 9500, 92093 La Jolla, CA, USA.
5
Department of Psychiatry, Uniformed Services University of the Health Sciences, Jones Bridge Road 4301, 20814 Bethesda, MD, USA.
6
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Danish Centre for Neonatal Screening, Department of Congenital Diseases, Statens Serum Institute, Artillerivej 5, DK-2300 Copenhagen, Denmark.
7
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Kirkeveien 166, 0450 Oslo, Norway.
8
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Institute of Biological Psychiatry, Mental Health Center St. Hans, Mental Health Services Copenhagen, Boserupvej 2, DK-4000 Roskilde, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
9
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Institute of Biological Psychiatry, Mental Health Center St. Hans, Mental Health Services Copenhagen, Boserupvej 2, DK-4000 Roskilde, Denmark; Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Kirkeveien 166, 0450 Oslo, Norway; Division of Biostatistics, Department of Family Medicine and Public Health, University of California, San Diego.
10
Research and Knowledge Center, The Danish Veteran Center, Garnisonen 1, 4100 Ringsted, Denmark.

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:

Cross-disorder genetic correlations; IL15; Inflammation; PTSD

PMID:
30999091
DOI:
10.1016/j.jad.2019.04.070

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