A GENOME-WIDE ASSOCIATION STUDY OF CLINICAL SYMPTOMS OF DISSOCIATION IN A TRAUMA-EXPOSED SAMPLE

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 x 10(-8)). The peak SNP was rs263232 (beta = 1.4, P = 6.12 x 10(-7)), located in the adenylyl cyclase 8 (ADCY8) gene; a second SNP in the suggestive range was rs71534169 (beta = 1.63, P = 3.79 x 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.