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A Preliminary Investigation of Rare Variants Associated With Genetic Risk for PTSD in a Natural Disaster-Exposed Adolescent Sample

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A Preliminary Investigation of Rare Variants Associated With Genetic Risk for PTSD in a Natural Disaster-Exposed Adolescent Sample

Christina M Sheerin et al. Eur J Psychotraumatol.

Abstract

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, M age = 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 p adj < .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.

Keywords: PTSD; adolescent risk; exome array; natural disaster; rare variants.

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Grant support

The main study was supported by NIMH under Grant R01 MH081056 (PI: Ruggiero). The genetic component was supported by supplement grant from NIMH, MH081056-01S1 (PI: Amstadter). Dr Sheerin’s time is funded by NIAAA grant K01 AA025692; Dr Amstadter’s time is partially funded by NIAAA grant K02 AA023239; Dr Bountress’s time was funded by NIMH grant T32 MH018869. Funding sources had no involvement in the design, analysis of data, writing of the report, or decision to submit this manuscript

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