A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample

Background: Posttraumatic stress disorder (PTSD) involves a complex interaction of biological, psychological, and social factors. Numerous studies have demonstrated genetic variation associated with the development of PTSD, primarily in adults. However, the contribution of low frequency and rare genetic variants to PTSD is unknown to date. Moreover, there is limited work on genetic risk for PTSD in child and adolescent populations. Objective: This preliminary study aimed to identify the low frequency and rare genetic variation that contributes to PTSD using an exome array. Method: This post-disaster, adolescent sample (n = 707, 51% females, Mage = 14.54) was assessed for PTSD diagnosis and symptom count following tornado exposure. Results: Gene-based models, covarying for ancestry principal components, age, sex, tornado severity, and previous trauma identified variants in four genes associated with diagnosis and 276 genes associated with symptom count (at padj < .001). Functional class analyses suggested an association with variants in the nonsense class (nonsynonymous variant that results in truncation of, and usually non-functional, protein) with both outcomes. An exploratory gene network pathway analysis showed a great number of significant genes involved in brain and immune function, illustrating the usefulness of downstream examination of gene-based findings that may point to relevant biological processes. Conclusions: While further investigation in larger samples is warranted, findings align with extant PTSD literature that has identified variants associated with biological conditions such as immune function.