title: A genome-wide association study of clinical symptoms of dissociation in a trauma-exposed sample.
abstract: BACKGROUND
  Recent work suggests that a subset of individuals with posttraumatic stress disorder (PTSD) exhibit marked dissociative symptoms, as defined by derealization and depersonalization. A dissociative subtype of PTSD was added to the diagnostic criteria listed in the Diagnostic and Statistical Manual of Mental Disorders, Version 5 (DSM-5) to capture this presentation of PTSD. This study examined genetic polymorphisms for association with the symptoms that define the dissociative subtype of PTSD using a genome-wide approach.
  
  
  METHODS
  The sample comprised 484 White, non-Hispanic, trauma-exposed veterans and their partners who were assessed for lifetime PTSD and dissociation using a structured clinical interview. The prevalence of PTSD was 60.5%. Single-nucleotide polymorphisms (SNPs) from across the genome were obtained from a 2.5 million SNP array.
  
  
  RESULTS
  Ten SNPs evidenced suggestive association with dissociation (P < 10(-5)). No SNPs met genome-wide significance criteria (P < 5 × 10(-8)). The peak SNP was rs263232 (β = 1.4, P = 6.12 × 10(-7)), located in the adenylyl cyclase 8 (ADCY8) gene; a second SNP in the suggestive range was rs71534169 (β = 1.63, P = 3.79 × 10(-6)), located in the dipeptidyl-peptidase 6 (DPP6) gene.
  
  
  CONCLUSIONS
  ADCY8 is integral for long-term potentiation and synaptic plasticity and is implicated in fear-related learning and memory and long-term memory consolidation. DPP6 is critical for synaptic integration and excitation. These genes may exert effects on basic sensory integration and cognitive processes that underlie dissociative phenomena.
authors.affiliation: National Center for PTSD, 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.forename: Ann M
authors.initials: AM
authors.lastname: Rasmusson
authors.forename: Karen S
authors.initials: KS
authors.lastname: Mitchell
authors.forename: Mark W
authors.initials: MW
authors.lastname: Logue
authors.forename: Clinton T
authors.initials: CT
authors.lastname: Baldwin
authors.forename: Mark W
authors.initials: MW
authors.lastname: Miller
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics*; D000328:Adult; D000368:Aged; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics*; D004213:Dissociative Disorders / Q000235:genetics* / Q000523:psychology; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics*; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000523:psychology; D014728:Veterans / Q000523:psychology / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D009419:Nerve Tissue Proteins; D015221:Potassium Channels; C503535:DPP6 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D000262:Adenylyl Cyclases; C118292:adenylyl cyclase 8
keywords: ADCY8, DPP6; dissociation; dissociative subtype; gene; genome-wide; posttraumatic stress disorder