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Impact of traumatic life events and polygenic risk scores for major depression and posttraumatic stress disorder on Iraq/Afghanistan Veterans.

Lipsky RK, Garrett ME, Dennis MF, VA Mid-Atlantic MIRECC Workgroup , Hauser MA, Beckham JC, Ashley-Koch AE, Kimbrel NA. Impact of traumatic life events and polygenic risk scores for major depression and posttraumatic stress disorder on Iraq/Afghanistan Veterans. Journal of psychiatric research. 2023 Feb 1; 158:15-19.

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Abstract:

Traumatic experiences and genetic heritability are among the most widely acknowledged risk factors leading to the development of psychopathology; including posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). The purpose of this study was to investigate if polygenic risk scores (PRS) among Veterans interacted with traumatic stress to predict PTSD and MDD. 1,389 Iraq-Afghanistan military service Veterans from the Mental Illness Research Education and Clinical Center dataset were analyzed. Genome-wide association study (GWAS) statistics were utilized to generate PRS for PTSD (PRS) and PRS for MDD (PRS) in order to analyze PRS-by-environment (PRSxE) with trauma exposure to predict PTSD and MDD diagnoses. Trauma exposure and PRS, were independently associated with a current PTSD diagnosis (p  <  0.001 and p  <  0.001, respectively). The interaction between trauma exposure and PRS to predict a current diagnosis of PTSD trended towards significance (p  =  0.053). Stratifying by trauma thresholds, among those within the lowest trauma load, the association of PRS with PTSD was found to be nominally significant (p  =  0.03). For a MDD diagnosis, there was a significant association with trauma exposure (p  <  0.001); and the association with PRS was found to be nominally significant (p  =  0.03). No significant PRSxE effects were found with MDD. Our findings corroborate previous research highlighting trauma exposure, and genetic heritability, as risk factors for the development of PTSD and MDD in a Veteran population. Additionally, findings suggest that genetic vulnerability may be less important as trauma exposure increases, with high levels of trauma likely to result in PTSD and MDD, regardless of genetic vulnerability.




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