title: RORA and posttraumatic stress trajectories: main effects and interactions with childhood physical abuse history.
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
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Epidemiology, Mailman School of Public Health, Columbia University New York, New York.
authors: Sarah R
authors: SR
authors: Lowe
authors: Department of Epidemiology, Mailman School of Public Health, Columbia University New York, New York.
authors: Jacquelyn L
authors: JL
authors: Meyers
authors: Department of Epidemiology, Boston University School of Public Health Boston, Massachusetts.
authors: Sandro
authors: S
authors: Galea
authors: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina Chapel Hill, North Carolina.
authors: Allison E
authors: AE
authors: Aiello
authors: Department of Psychology, University of Illinois Urbana-Champaign Champaign, Illinois ; Institute for Genomic Biology, University of Illinois Urbana-Champaign Urbana, Illinois.
authors: Monica
authors: M
authors: Uddin
authors: Institute for Genomic Biology, University of Illinois Urbana-Champaign Urbana, Illinois ; Depratment of Molecular and Integrative Physiology, University of Illinois Urbana-Champaign Urbana, Illinois.
authors: Derek E
authors: DE
authors: Wildman
authors: Department of Epidemiology, Mailman School of Public Health, Columbia University New York, New York.
authors: Karestan C
authors: KC
authors: Koenen
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics*; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000523:psychology; D014504:Urban Health
chemical_list: D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human
keywords: Childhood physical abuse; gene-environment interaction; longitudinal survey; posttraumatic stress disorders; retinoid-related orphan receptor-alpha