title: Genome-wide Association Studies of Posttraumatic Stress Disorder in 2 Cohorts of US Army Soldiers.
abstract: Posttraumatic stress disorder (PTSD) is a prevalent, serious public health concern, particularly in the military. The identification of genetic risk factors for PTSD may provide important insights into the biological foundation of vulnerability and comorbidity.
  
  
  
  To discover genetic loci associated with the lifetime risk for PTSD in 2 cohorts from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).
  
  
  
  Two coordinated genome-wide association studies of mental health in the US military contributed participants. The New Soldier Study (NSS) included 3167 unique participants with PTSD and 4607 trauma-exposed control individuals; the Pre/Post Deployment Study (PPDS) included 947 unique participants with PTSD and 4969 trauma-exposed controls. The NSS data were collected from February 1, 2011, to November 30, 2012; the PDDS data, from January 9 to April 30, 2012. The primary analysis compared lifetime DSM-IV PTSD cases with trauma-exposed controls without lifetime PTSD. Data were analyzed from March 18 to December 27, 2015.
  
  
  
  Association analyses for PTSD used logistic regression models within each of 3 ancestral groups (European, African, and Latino American) by study, followed by meta-analysis. Heritability and genetic correlation and pleiotropy with other psychiatric and immune-related disorders were estimated.
  
  
  
  The NSS population was 80.7% male (6277 of 7774 participants; mean [SD] age, 20.9 [3.3] years); the PPDS population, 94.4% male (5583 of 5916 participants; mean [SD] age, 26.5 [6.0] years). A genome-wide significant locus was found in ANKRD55 on chromosome 5 (rs159572; odds ratio [OR], 1.62; 95% CI, 1.37-1.92; P = 2.34 × 10-8) and persisted after adjustment for cumulative trauma exposure (adjusted OR, 1.64; 95% CI, 1.39-1.95; P = 1.18 × 10-8) in the African American samples from the NSS. A genome-wide significant locus was also found in or near ZNF626 on chromosome 19 (rs11085374; OR, 0.77; 95% CI, 0.70-0.85; P = 4.59 × 10-8) in the European American samples from the NSS. Similar results were not found for either single-nucleotide polymorphism in the corresponding ancestry group from the PPDS sample, in other ancestral groups, or in transancestral meta-analyses. Single-nucleotide polymorphism-based heritability was nonsignificant, and no significant genetic correlations were observed between PTSD and 6 mental disorders or 9 immune-related disorders. Significant evidence of pleiotropy was observed between PTSD and rheumatoid arthritis and, to a lesser extent, psoriasis.
  
  
  
  In the largest genome-wide association study of PTSD to date, involving a US military sample, limited evidence of association for specific loci was found. Further efforts are needed to replicate the genome-wide significant association with ANKRD55-associated in prior research with several autoimmune and inflammatory disorders-and to clarify the nature of the genetic overlap observed between PTSD and rheumatoid arthritis and psoriasis.
authors.affiliation: Department of Psychiatry, University of California, San Diego (UCSD), La Jolla2Department of Family Medicine and Public Health, UCSD, La Jolla3Psychiatry Service, Veterans Affairs San Diego Healthcare System, San Diego, California.
authors.forename: Murray B
authors.initials: MB
authors.lastname: Stein
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston5Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ursano
authors.affiliation: Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Tianxi
authors.initials: T
authors.lastname: Cai
authors.affiliation: Department of Psychiatry, Yale University, New Haven, Connecticut9Department of Genetics, Yale University, New Haven, Connecticut10Department of Neurobiology, Yale University, New Haven, Connecticut.
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.affiliation: Institute for Social Research, University of Michigan, Ann Arbor.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Heeringa
authors.affiliation: Department of Family Medicine and Public Health, UCSD, La Jolla.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of Psychiatry, Yale University, New Haven, Connecticut.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Jensen
authors.affiliation: Department of Psychiatry, University of California, San Diego (UCSD), La Jolla.
authors.forename: Adam X
authors.initials: AX
authors.lastname: Maihofer
authors.affiliation: Institute for Social Research, University of Michigan, Ann Arbor.
authors.forename: Colter
authors.initials: C
authors.lastname: Mitchell
authors.affiliation: Department of Psychiatry, University of California, San Diego (UCSD), La Jolla.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Nievergelt
authors.affiliation: Department of Psychology, Harvard University, Cambridge, Massachusetts.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Nock
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Neale
authors.affiliation: Department of Psychiatry, Yale University, New Haven, Connecticut9Department of Genetics, Yale University, New Haven, Connecticut10Department of Neurobiology, Yale University, New Haven, Connecticut.
authors.forename: Renato
authors.initials: R
authors.lastname: Polimanti
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ripke
authors.affiliation: Department of Family Medicine and Public Health, UCSD, La Jolla.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Psychiatry, University of California, San Diego (UCSD), La Jolla.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Thomas
authors.affiliation: Department of Psychiatry, Yale University, New Haven, Connecticut9Department of Genetics, Yale University, New Haven, Connecticut10Department of Neurobiology, Yale University, New Haven, Connecticut13currently with Department of Computational Biology and.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute for Social Research, University of Michigan, Ann Arbor.
authors.forename: Erin B
authors.initials: EB
authors.lastname: Ware
authors.affiliation: National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
authors.forename: Susan
authors.initials: S
authors.lastname: Borja
authors.affiliation: Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Kessler
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston5Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge.
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008889:Military Personnel / Q000523:psychology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000523:psychology*; D055815:Young Adult
chemical_list: C584515:ANKRD55 protein, human; D002352:Carrier Proteins