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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 gen...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896412/ https://www.ncbi.nlm.nih.gov/pubmed/31839899 http://dx.doi.org/10.1080/20008198.2019.1688935 |
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author | Sheerin, Christina M. Vladimirov, Vladimir Williamson, Vernell Bountress, Kaitlin K. Danielson, Carla Ruggiero, Kenneth Amstadter, Ananda B. |
author_facet | Sheerin, Christina M. Vladimirov, Vladimir Williamson, Vernell Bountress, Kaitlin K. Danielson, Carla Ruggiero, Kenneth Amstadter, Ananda B. |
author_sort | Sheerin, Christina M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6896412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-68964122019-12-13 A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample Sheerin, Christina M. Vladimirov, Vladimir Williamson, Vernell Bountress, Kaitlin K. Danielson, Carla Ruggiero, Kenneth Amstadter, Ananda B. Eur J Psychotraumatol Clinical Research Article 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. Taylor & Francis 2019-12-02 /pmc/articles/PMC6896412/ /pubmed/31839899 http://dx.doi.org/10.1080/20008198.2019.1688935 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Research Article Sheerin, Christina M. Vladimirov, Vladimir Williamson, Vernell Bountress, Kaitlin K. Danielson, Carla Ruggiero, Kenneth Amstadter, Ananda B. A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample |
title | A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample |
title_full | A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample |
title_fullStr | A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample |
title_full_unstemmed | A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample |
title_short | A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample |
title_sort | preliminary investigation of rare variants associated with genetic risk for ptsd in a natural disaster-exposed adolescent sample |
topic | Clinical Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896412/ https://www.ncbi.nlm.nih.gov/pubmed/31839899 http://dx.doi.org/10.1080/20008198.2019.1688935 |
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