RORA and Posttraumatic Stress Trajectories: Main Effects and Interactions with Childhood Physical Abuse History.

Sarah R. Lowe, Montclair State University
Jacquelyn L. Meyers, Columbia University - Mailman School of Public Health
Sandro Galea, Boston University School of Health
Allison E. Aiello, University of North Carolina at Chapel Hill
Monica Uddin, University of Illinois at Urbana-Champaign
Derek E. Wildman, University of Illinois at Urbana-Champaign
Karestan C. Koenen, Columbia University - Mailman School of Public Health

Brain Behav. 2015 Apr; 5(4): e00323. Published online 2015 Mar 8. doi: [10.1002/brb3.323]



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.


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.


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.


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.