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Original Investigation
October 2014

Interaction of the ADRB2 Gene Polymorphism With Childhood Trauma in Predicting Adult Symptoms of Posttraumatic Stress Disorder

Author Affiliations
  • 1Department of Psychiatry, University of Michigan, Ann Arbor
  • 2Veterans Affairs Ann Arbor Health System, Ann Arbor, Michigan
  • 3Emory University, Atlanta, Georgia
  • 4The Johns Hopkins University, Baltimore, Maryland
  • 5Columbia University, New York, New York
  • 6University of Toledo, Toledo, Ohio
  • 7Case Western University, Cleveland, Ohio
JAMA Psychiatry. 2014;71(10):1174-1182. doi:10.1001/jamapsychiatry.2014.999

Importance  Posttraumatic stress disorder (PTSD), while highly prevalent (7.6% over a lifetime), develops only in a subset of trauma-exposed individuals. Genetic risk factors in interaction with trauma exposure have been implicated in PTSD vulnerability.

Objective  To examine the association of 3755 candidate gene single-nucleotide polymorphisms with PTSD development in interaction with a history of childhood trauma.

Design, Setting, and Participants  Genetic association study in an Ohio National Guard longitudinal cohort (n = 810) of predominantly male soldiers of European ancestry, with replication in an independent Grady Trauma Project (Atlanta, Georgia) cohort (n = 2083) of predominantly female African American civilians.

Main Outcomes and Measures  Continuous measures of PTSD severity, with a modified (interview) PTSD checklist in the discovery cohort and the PTSD Symptom Scale in the replication cohort.

Results  Controlling for the level of lifetime adult trauma exposure, we identified the novel association of a single-nucleotide polymorphism within the promoter region of the ADRB2 (Online Mendelian Inheritance in Man 109690) gene with PTSD symptoms in interaction with childhood trauma (rs2400707, P = 1.02 × 10−5, significant after correction for multiple comparisons). The rs2400707 A allele was associated with relative resilience to childhood adversity. An rs2400707 × childhood trauma interaction predicting adult PTSD symptoms was replicated in the independent predominantly female African American cohort.

Conclusions and Relevance  Altered adrenergic and noradrenergic function has been long believed to have a key etiologic role in PTSD development; however, direct evidence of this link has been missing. The rs2400707 polymorphism has been linked to function of the adrenergic system, but, to our knowledge, this is the first study to date linking the ADRB2 gene to PTSD or any psychiatric disorders. These findings have important implications for PTSD etiology, chronic pain, and stress-related comorbidity, as well as for both primary prevention and treatment strategies.