Genomic Predictors of Combat Stress Vulnerability and Resilience

The Genomic Predictors of Combat Stress Vulnerability and Resilience Study was designed to probe the likely hereditary basis for risk or resilience to develop PTSD and other trauma spectrum disorders. The overall guiding hypothesis was that genomic variation gives rise to risk/susceptibility traits that, when actuated by traumatic environmental stimuli, such as combat, give rise to PTSD and other stress-related phenotypes. Two studies designed to identify risk and resilience factors for combat-induced, stress-related symptoms are being conducted by our group: The Marine Resiliency Study (MRS) is a prospective PTSD study with longitudinal follow-up (pre- and post-exposure to combat stress) of US Marines bound for deployment to Iraq or Afghanistan. Extensive phenotyping includes 3 domains: Psychosocial, Psychophysiologic, and Biophysiologic. The biological and physiological measures collected were chosen in part due to their potential to serve as intermediate phenotypes for stress-related disorders. A second, cross-sectional study involves a cohort of combat-exposed active duty or previously deployed service members (CAVC), including PTSD cases and controls with comparable psychosocial and clinical phenotypes. Little information is available about the factors that explain why some trauma survivors develop stress disorders and some do not. It is hoped that the insights gained from this approach will improve understanding of the genetic contributors to PTSD, and potentially provide novel diagnostic tests and therapeutic approaches to this currently enigmatic and difficult-to-manage condition.]]>
We recruited a cohort of 3,830 veterans who were evaluated for PTSD. All subjects met criteria A for PTSD. Cases were designated as those who met the DSM-IV definition for PTSD (including the A1 criteria, but not A2) and controls were those who did not. Subjects were genotyped on Illumina HumanOmniExpressExome arrays (on two platforms). Each subject's ancestry was genetically determined and subjects were clustered into one of four ancestral subgroups: European (N=2,356), African (N=232), Hispanic/Native American (N=708), or other (including East Asian; N=534). GWAS for PTSD were run on each ancestral subgroup. The association results presented are from a meta-analysis of GWAS results across all subgroupsMarine Resiliency Study (MRS): Inclusion criteria: all deploying Marines in units selected for the study. Exclusion criterion: none, except that Marines who do not want to participate will not be included. Active duty or previously deployed service members (CAVC): Inclusion Criteria: Evidence of combat as defined by the following: (a) a history of deployment to a combat zone, as evidenced by service record (b) a CES score of at least 10 (Keane et. al. 1989), (c) Trauma exposure sufficient to meet Category A of PTSD criteria (Breslau and Kessler 2001). Case Inclusion Criteria: Diagnosis of PTSD as determined by Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) diagnosis (Spitzer R.L. and Williams J. 1983). Control Inclusion Criteria: A structured Clinical Interview for DSM-IV Axis I Disorders (SCID) with No PTSD diagnosis (Spitzer R.L. and Williams J. 1983). Exclusion Criteria:(1) Younger than age 18 or older than 65 years of age; (2) Inability or unwillingness to give informed consent; (3) A primary diagnoses other than PTSD as determined by Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) (Spitzer R.L. and Williams J. 1983). Breslau,N, Kessler,RC (2001): The stressor criterion in DSM-IV posttraumatic stress disorder: an empirical investigation. Biol.Psychiatry 50: 699-704. Keane,TM, Fairbank,JA, Caddell JM, Zimering RT, Taylor KI, Mora CA (1989): Brief Reports: clinical evaluation of a measure to assess combat exposure. J consult Clin Psychol 1: 53-55. Spitzer,RL, Williams,J (1983): Instructional Manual for SCID. New York: New York State Psychiatric Institute.]]>
May 2005 - Beginning of sample collection July 2011 - GWAS funded October 2013 - End of sample collection ]]>