Polygenic risk for traumatic loss-related PTSD in US military veterans: Protective effect of secure attachment style

To examine whether attachment style moderates the relationship between polygenic risk scores (PRS) for posttraumatic stress disorder (PTSD) re-experiencing (PTSD_REX) symptoms and the severity of and positive screen for traumatic loss-related PTSD. Data were analysed from 631 US veterans who endorsed ‘unexpected death of a loved one’ as their ‘worst’ traumatic event. Multivariable models evaluated the association between PRS for PTSD_REX, attachment style, and their interaction in predicting severity and positive screen for PTSD. A gene enrichment analysis was conducted to identify possible molecular mechanisms underlying the association between PTSD_REX PRS and PTSD. PTSD_REX PRS (<i>β</i> = 0.17; odds ratio [OR] = 1.85), attachment style (<i>β</i>= −0.33; OR = 0.14), and PTSD_REX PRS × attachment style interaction (<i>β</i>= −0.12; OR = 0.53) were significant predictors of the severity and positive screen for PTSD. The most significant gene set detected was the gene ontology (GO) cellular component podosome set (GO:0002102, <i>p</i> −5). Having a secure attachment style may help mitigate polygenic risk for developing traumatic loss-related PTSD in US veterans. Podosomes, which are implicated in inflammatory and neuroplasticity processes, may contribute to the genetic liability to developing loss-related PTSD. Psychological treatments targeting attachment security may help mitigate increased polygenic risk for loss-related PTSD in this population.