Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder

Zachary A Kaminsky, Holly Wilcox, William W Eaton, K. Van Eck, V. Kilaru, T. Jovanovic, T. Klengel, B. Bradley, E. B. Binder, K. J. Ressler, A. K. Smith

Research output: Contribution to journalArticle

Abstract

Traumatic stress results in hypothalamic pituitary adrenal (HPA) axis abnormalities and an increased risk to both suicidal behaviors and post-traumatic stress disorder (PTSD). Previous work out of our laboratory identified SKA2 DNA methylation associations with suicidal behavior in the blood and brain of multiple cohorts. Interaction of SKA2 with stress predicted suicidal behavior with ~ 80% accuracy. SKA2 is hypothesized to reduce the ability to suppress cortisol following stress, which is of potentially high relevance in traumatized populations. Our objective was to investigate the interaction of SKA2 and trauma exposure on HPA axis function, suicide attempt and PTSD. SKA2 DNA methylation at Illumina HM450 probe cg13989295 was assessed for association with suicidal behavior and PTSD metrics in the context of Child Trauma Questionnaire (CTQ) scores in 421 blood and 61 saliva samples from the Grady Trauma Project (GTP) cohort. Dexamethasone suppression test (DST) data were evaluated for a subset of 209 GTP subjects. SKA2 methylation interacted with CTQ scores to predict lifetime suicide attempt in saliva and blood with areas under the receiver operator characteristic curve (AUCs) of 0.76 and 0.73 (95% confidence interval (CI): 0.60.92, P = 0.003, and CI: 0.650.78, P<0.0001) and to mediate the suppression of cortisol following DST (β = 0.5 ± 0.19, F = 1.51, degrees of freedom (df) = 12/167, P = 0.0096). Cumulatively, the data suggest that epigenetic variation at SKA2 mediates vulnerability to suicidal behaviors and PTSD through dysregulation of the HPA axis in response to stress.

Original languageEnglish (US)
Article numbere627
JournalTranslational Psychiatry
Volume5
Issue number8
DOIs
StatePublished - Aug 25 2015

Fingerprint

Post-Traumatic Stress Disorders
Epigenomics
Wounds and Injuries
DNA Methylation
Saliva
Suicide
Dexamethasone
Hydrocortisone
Confidence Intervals
Aptitude
Methylation
Area Under Curve
Brain
Population
Surveys and Questionnaires

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder. / Kaminsky, Zachary A; Wilcox, Holly; Eaton, William W; Van Eck, K.; Kilaru, V.; Jovanovic, T.; Klengel, T.; Bradley, B.; Binder, E. B.; Ressler, K. J.; Smith, A. K.

In: Translational Psychiatry, Vol. 5, No. 8, e627, 25.08.2015.

Research output: Contribution to journalArticle

Kaminsky, ZA, Wilcox, H, Eaton, WW, Van Eck, K, Kilaru, V, Jovanovic, T, Klengel, T, Bradley, B, Binder, EB, Ressler, KJ & Smith, AK 2015, 'Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder', Translational Psychiatry, vol. 5, no. 8, e627. https://doi.org/10.1038/tp.2015.105
Kaminsky, Zachary A ; Wilcox, Holly ; Eaton, William W ; Van Eck, K. ; Kilaru, V. ; Jovanovic, T. ; Klengel, T. ; Bradley, B. ; Binder, E. B. ; Ressler, K. J. ; Smith, A. K. / Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder. In: Translational Psychiatry. 2015 ; Vol. 5, No. 8.
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