RORA and posttraumatic stress trajectories: Main effects and interactions with childhood physical abuse history

Sarah Lowe, Jacquelyn L. Meyers, Sandro Galea, Allison E. Aiello, Monica Uddin, Derek E. Wildman, Karestan C. Koenen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Longitudinal studies of posttraumatic stress (PTS) have documented environmental factors as predictors of trajectories of higher, versus lower, symptoms, among them experiences of childhood physical abuse. Although it is now well-accepted that genes and environments jointly shape the risk of PTS, no published studies have investigated genes, or gene-by-environment interactions (GxEs), as predictors of PTS trajectories. The purpose of this study was to fill this gap. Methods and Materials: We examined associations between variants of the retinoid-related orphan receptor alpha (RORA) gene and trajectory membership among a sample of predominantly non-Hispanic Black urban adults (N = 473). The RORA gene was selected based on its association with posttraumatic stress disorder (PTSD) in the first PTSD genome wide association study. Additionally, we explored GxEs between RORA variants and childhood physical abuse history. Results: We found that the minor allele of the RORA SNP rs893290 was a significant predictor of membership in a trajectory of consistently high PTS, relatively to a trajectory of consistently low PTS. Additionally, the GxE of rs893290 with childhood physical abuse was significant. Decomposition of the interaction showed that minor allele frequency was more strongly associated with membership in consistently high or decreasing PTS trajectories, relative to a consistently low PTS trajectory, among participants with higher levels of childhood physical abuse. Conclusion: The results of the study provide preliminary evidence that variation in the RORA gene is associated with membership in trajectories of higher PTS and that these associations are stronger among persons exposed to childhood physical abuse. Replication and analysis of functional data are needed to further our understanding of how RORA relates to PTS trajectories.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalBrain and Behavior
Volume5
Issue number4
DOIs
StatePublished - 1 Apr 2015

Fingerprint

Orphaned Children
Genes
Post-Traumatic Stress Disorders
Nuclear Receptor Subfamily 1, Group F, Member 1
Gene-Environment Interaction
Genome-Wide Association Study
Gene Frequency
Single Nucleotide Polymorphism
Longitudinal Studies
Alleles
Physical Abuse

Keywords

  • Childhood physical abuse
  • Gene-environment interaction
  • Longitudinal survey
  • Posttraumatic stress disorders
  • Retinoid-related orphan receptor-alpha

Cite this

Lowe, S., Meyers, J. L., Galea, S., Aiello, A. E., Uddin, M., Wildman, D. E., & Koenen, K. C. (2015). RORA and posttraumatic stress trajectories: Main effects and interactions with childhood physical abuse history. Brain and Behavior, 5(4), 1-11. https://doi.org/10.1002/brb3.323
Lowe, Sarah ; Meyers, Jacquelyn L. ; Galea, Sandro ; Aiello, Allison E. ; Uddin, Monica ; Wildman, Derek E. ; Koenen, Karestan C. / RORA and posttraumatic stress trajectories : Main effects and interactions with childhood physical abuse history. In: Brain and Behavior. 2015 ; Vol. 5, No. 4. pp. 1-11.
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Lowe, S, Meyers, JL, Galea, S, Aiello, AE, Uddin, M, Wildman, DE & Koenen, KC 2015, 'RORA and posttraumatic stress trajectories: Main effects and interactions with childhood physical abuse history', Brain and Behavior, vol. 5, no. 4, pp. 1-11. https://doi.org/10.1002/brb3.323

RORA and posttraumatic stress trajectories : Main effects and interactions with childhood physical abuse history. / Lowe, Sarah; Meyers, Jacquelyn L.; Galea, Sandro; Aiello, Allison E.; Uddin, Monica; Wildman, Derek E.; Koenen, Karestan C.

In: Brain and Behavior, Vol. 5, No. 4, 01.04.2015, p. 1-11.

Research output: Contribution to journalArticle

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T1 - RORA and posttraumatic stress trajectories

T2 - Main effects and interactions with childhood physical abuse history

AU - Lowe, Sarah

AU - Meyers, Jacquelyn L.

AU - Galea, Sandro

AU - Aiello, Allison E.

AU - Uddin, Monica

AU - Wildman, Derek E.

AU - Koenen, Karestan C.

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N2 - Background: Longitudinal studies of posttraumatic stress (PTS) have documented environmental factors as predictors of trajectories of higher, versus lower, symptoms, among them experiences of childhood physical abuse. Although it is now well-accepted that genes and environments jointly shape the risk of PTS, no published studies have investigated genes, or gene-by-environment interactions (GxEs), as predictors of PTS trajectories. The purpose of this study was to fill this gap. Methods and Materials: We examined associations between variants of the retinoid-related orphan receptor alpha (RORA) gene and trajectory membership among a sample of predominantly non-Hispanic Black urban adults (N = 473). The RORA gene was selected based on its association with posttraumatic stress disorder (PTSD) in the first PTSD genome wide association study. Additionally, we explored GxEs between RORA variants and childhood physical abuse history. Results: We found that the minor allele of the RORA SNP rs893290 was a significant predictor of membership in a trajectory of consistently high PTS, relatively to a trajectory of consistently low PTS. Additionally, the GxE of rs893290 with childhood physical abuse was significant. Decomposition of the interaction showed that minor allele frequency was more strongly associated with membership in consistently high or decreasing PTS trajectories, relative to a consistently low PTS trajectory, among participants with higher levels of childhood physical abuse. Conclusion: The results of the study provide preliminary evidence that variation in the RORA gene is associated with membership in trajectories of higher PTS and that these associations are stronger among persons exposed to childhood physical abuse. Replication and analysis of functional data are needed to further our understanding of how RORA relates to PTS trajectories.

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KW - Gene-environment interaction

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