title: EPIGENETIC VARIATION AT SKA2 PREDICTS SUICIDE PHENOTYPES AND INTERNALIZING PSYCHOPATHOLOGY.
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.
authors.affiliation: National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, Massachusetts.|Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sadeh
authors.affiliation: National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, Massachusetts.|Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Wolf
authors.affiliation: Research Service, VA Boston Healthcare System, Boston, Massachusetts.|Biomedical Genetics, Boston University School of Medicine, Boston, Massachusetts.|Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Logue
authors.affiliation: National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, Massachusetts.|Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Jasmeet P
authors.initials: JP
authors.lastname: Hayes
authors.affiliation: Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Arkansas.
authors.forename: Annjanette
authors.initials: A
authors.lastname: Stone
authors.affiliation: Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Arkansas.
authors.forename: L Michelle
authors.initials: LM
authors.lastname: Griffin
authors.affiliation: Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Arkansas.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Schichman
authors.affiliation: National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, Massachusetts.|Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Miller
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007389:Internal-External Control; D008297:Male; D001523:Mental Disorders / Q000235:genetics* / Q000523:psychology*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D059020:Suicidal Ideation; D013405:Suicide / Q000523:psychology*; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data; D014728:Veterans / Q000523:psychology / Q000706:statistics & numerical data
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C516428:SKA2 protein, human
keywords: DNA methylation; PTSD; externalizing; suicide risk; trauma; veterans