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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Post-traumatic stress following military deployment: Genetic associations and cross-disorder genetic correlations

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  1. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

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  2. Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants

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  3. Clinical association to FKBP5 rs1360780 in patients with depression

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  4. A large-scale genomic investigation of susceptibility to infection and its association with mental disorders in the Danish population

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  5. Genetic risk scores for major psychiatric disorders and the risk of postpartum psychiatric disorders

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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 languageEnglish
JournalJournal of Affective Disorders
Volume252
Pages (from-to)350-357
Number of pages8
ISSN0165-0327
DOIs
Publication statusPublished - 1 Jun 2019

ID: 58594201