Can Genetic Perturbations of Inflammatory Response Contribute to the Risk of PTSD?

Research Paper Title

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

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 aetiology, the biological mechanisms underlying risk and development of PTSD remain unknown.

Methods

Here, the researchers 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.

They perform integrated analyses of our results with gene-expression and chromatin-contact datasets to prioritised genes. They also leverage on other large GWAS (N>300,000) to investigate genetic correlations between PTSD and other psychiatric disorders and traits.

Results

They discover, but do not replicate, one region, 4q31, close to the IL15 gene, which is genome-wide significantly associated with PTSD. They 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.

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

Conclusions

The 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.

Reference

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, pp.350-357. doi: 10.1016/j.jad.2019.04.070. Epub 2019 Apr 9.

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