title: SLC6A4 methylation modifies the effect of the number of traumatic events on risk for posttraumatic stress disorder.
abstract: BACKGROUND
  Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder that occurs following exposure to a traumatic event. However, most individuals do not develop PTSD following even a severe trauma, leading to a search for new variables, such as genetic and other molecular variation, associated with vulnerability and resilience in the face of trauma exposure.
  
  
  METHODS
  We examined whether serotonin transporter (SLC6A4) promoter genotype and methylation status modified the association between number of traumatic events experienced and PTSD in a subset of 100 individuals from the Detroit Neighborhood Health Study.
  
  
  RESULTS
  Number of traumatic events was strongly associated with risk of PTSD. Neither SLC6A4 genotype nor methylation status was associated with PTSD in main effects models. However, SLC6A4 methylation levels modified the effect of the number of traumatic events on PTSD after controlling for SLC6A4 genotype. Persons with more traumatic events were at increased risk for PTSD, but only at lower methylation levels. At higher methylation levels, individuals with more traumatic events were protected from this disorder. This interaction was observed whether the outcome was PTSD diagnosis, symptom severity, or number of symptoms.
  
  
  CONCLUSIONS
  Gene-specific methylation patterns may offer potential molecular signatures of increased risk for and resilience to PTSD.
authors: Departments of Society, Human Development, and Health and Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. kkoenen@hsph.harvard.edu
authors: Karestan C
authors: KC
authors: Koenen
authors: Monica
authors: M
authors: Uddin
authors: Shun-Chiao
authors: SC
authors: Chang
authors: Allison E
authors: AE
authors: Aiello
authors: Derek E
authors: DE
authors: Wildman
authors: Emily
authors: E
authors: Goldmann
authors: Sandro
authors: S
authors: Galea
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