Naomi Sadeh1,2, Erika J Wolf1,2, Mark W Logue3,4,5, Jasmeet P Hayes1,2, Annjanette Stone6, L Michelle Griffin6, Steven A Schichman6, Mark W Miller1,2. 1. National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, Massachusetts. 2. Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts. 3. Research Service, VA Boston Healthcare System, Boston, Massachusetts. 4. Biomedical Genetics, Boston University School of Medicine, Boston, Massachusetts. 5. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts. 6. Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Arkansas.
Abstract
BACKGROUND: DNA methylation of the SKA2 gene has recently been implicated as a biomarker of suicide risk and posttraumatic stress disorder (PTSD). To examine the specificity and reliability of these findings, we examined associations between SKA2 DNA methylation, broad dimensions of psychiatric symptoms, and suicide phenotypes in adults with high levels of trauma exposure. METHODS: A total of 466 White, non-Hispanic veterans and their intimate partners (65% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis. DNA methylation of the CpG locus cg13989295 and genotype at the methylation-associated single-nucleotide polymorphism (SNP) rs7208505 were examined in relation to current and lifetime PTSD, internalizing and externalizing psychopathology, and suicide phenotypes (ideation, plans, and attempts). RESULTS: DNA methylation at the previously implicated SKA2 CpG locus (cg13989295) was associated with current and lifetime symptoms of internalizing (but not externalizing) disorders. SKA2 methylation levels also predicted higher rates of current suicidal thoughts and behaviors, even after including well-established psychiatric risk factors for suicide in the model. Associations between PTSD and SKA2 were not significant, and genetic variation at the methylation-associated SNP (rs7208505) was not related to any of the phenotypes examined. CONCLUSIONS: SKA2 methylation may index a general propensity to experience stress-related psychopathology, including internalizing disorders and suicidal thoughts and behaviors. This study demonstrates that SKA2 methylation levels explain unique variance in suicide risk not captured by clinical symptom interviews, providing further evidence of its potential utility as a biomarker of suicide risk and stress-related psychopathology.
BACKGROUND: DNA methylation of the SKA2 gene has recently been implicated as a biomarker of suicide risk and posttraumatic stress disorder (PTSD). To examine the specificity and reliability of these findings, we examined associations between SKA2 DNA methylation, broad dimensions of psychiatric symptoms, and suicide phenotypes in adults with high levels of trauma exposure. METHODS: A total of 466 White, non-Hispanic veterans and their intimate partners (65% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis. DNA methylation of the CpG locus cg13989295 and genotype at the methylation-associated single-nucleotide polymorphism (SNP) rs7208505 were examined in relation to current and lifetime PTSD, internalizing and externalizing psychopathology, and suicide phenotypes (ideation, plans, and attempts). RESULTS: DNA methylation at the previously implicated SKA2 CpG locus (cg13989295) was associated with current and lifetime symptoms of internalizing (but not externalizing) disorders. SKA2 methylation levels also predicted higher rates of current suicidal thoughts and behaviors, even after including well-established psychiatric risk factors for suicide in the model. Associations between PTSD and SKA2 were not significant, and genetic variation at the methylation-associated SNP (rs7208505) was not related to any of the phenotypes examined. CONCLUSIONS:SKA2 methylation may index a general propensity to experience stress-related psychopathology, including internalizing disorders and suicidal thoughts and behaviors. This study demonstrates that SKA2 methylation levels explain unique variance in suicide risk not captured by clinical symptom interviews, providing further evidence of its potential utility as a biomarker of suicide risk and stress-related psychopathology.
Authors: Marco P Boks; Bart P F Rutten; Elbert Geuze; Lotte C Houtepen; Eric Vermetten; Zachary Kaminsky; Christiaan H Vinkers Journal: Neuropsychopharmacology Date: 2015-09-11 Impact factor: 7.853
Authors: Lisa Rice; Charlotte E Waters; Jennifer Eccles; Helen Garside; Paula Sommer; Paul Kay; Fiona H Blackhall; Leo Zeef; Brian Telfer; Ian Stratford; Rob Clarke; Dave Singh; Adam Stevens; Anne White; David W Ray Journal: J Endocrinol Date: 2008-06-26 Impact factor: 4.286
Authors: Zhenwei Zhou; Kathryn L Lunetta; Alicia K Smith; Erika J Wolf; Annjanette Stone; Steven A Schichman; Regina E McGlinchey; William P Milberg; Mark W Miller; Mark W Logue Journal: Epigenomics Date: 2019-06-26 Impact factor: 4.778
Authors: Makena L Clive; Marco P Boks; Christiaan H Vinkers; Lauren M Osborne; Jennifer L Payne; Kerry J Ressler; Alicia K Smith; Holly C Wilcox; Zachary Kaminsky Journal: Clin Epigenetics Date: 2016-11-03 Impact factor: 6.551