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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Depression / genetics
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Military Personnel / psychology*
  • Multifactorial Inheritance
  • Occupational Diseases / genetics*
  • Occupational Diseases / psychology*
  • Schizophrenia / genetics
  • Sleep Initiation and Maintenance Disorders / genetics
  • Sleep Initiation and Maintenance Disorders / psychology
  • Stress Disorders, Post-Traumatic / genetics*
  • Stress Disorders, Post-Traumatic / psychology*