International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

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  • Adam X. Maihofer, VA San Diego Healthcare System
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  • Torsten Klengel, University of Göttingen
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  • Elizabeth G. Atkinson, Massachusetts General Hospital, Boston
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  • Chia Yen Chen, Massachusetts General Hospital, Boston
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  • Karmel W. Choi, Harvard School of Public Health
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  • Jonathan R.I. Coleman, King's College London
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  • Shareefa Dalvie, University of Cape Town
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  • Laramie E. Duncan, Stanford University, Stanford, California
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  • Joel Gelernter, Department of Veterans Affairs
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  • Daniel F. Levey, Yale School of Medicine
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  • Mark W. Logue, Department of Veterans Affairs
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  • Renato Polimanti, Yale School of Medicine
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  • Allison C. Provost, Cohen Veterans Bioscience
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  • Andrew Ratanatharathorn, Harvard School of Public Health
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  • Murray B. Stein, VA San Diego Healthcare System
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  • Katy Torres, VA San Diego Healthcare System
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  • Allison E. Aiello, Gillings School of Global Public Health
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  • Lynn M. Almli, Emory University
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  • Ananda B. Amstadter, Virginia Commonwealth University
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  • Søren B. Andersen, The Danish Veteran Centre, Research and Knowledge Centre
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  • Ole A. Andreassen, Universitetet i Oslo
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  • Paul A. Arbisi, Department of Veterans Affairs
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  • Allison E. Ashley-Koch, Duke University
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  • S. Bryn Austin, Harvard School of Public Health
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  • Esmina Avdibegovic, University Clinical Center of Tuzla
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  • Dragan Babić, University Clinical Center of Mostar
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  • Marie Bækvad-Hansen, Statens Serum Institut, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
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  • Dewleen G. Baker, VA San Diego Healthcare System
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  • Jean C. Beckham, Duke University, Genetics Research Laboratory
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  • Laura J. Bierut, Internal Medicine, Washington University in St. Louis, School of Medicine
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  • Jonathan I. Bisson, Cardiff University
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  • Marco P. Boks, Utrecht University
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  • Elizabeth A. Bolger, Harvard University
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  • Bekh Bradley, Emory University, Atlanta VA Health Care System
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  • Megan Brashear, Louisiana State University Health Sciences Center
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  • Gerome Breen, King's College London
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  • Richard A. Bryant, University of New South Wales (UNSW) Australia
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  • Angela C. Bustamante, University of Michigan, Ann Arbor
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  • Jonas Bybjerg-Grauholm, Statens Serum Institut, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
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  • José M. Caldas- de- Almeida, Lisbon Institute of Global Mental Health
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  • Anders M. Dale, University of California, San Diego
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  • Mark J. Daly, Massachusetts General Hospital, Boston
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  • Nikolaos P. Daskalakis, Harvard Medical School, Harvard University, Cohen Veterans Bioscience, Icahn School of Medicine at Mount Sinai
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  • Jürgen Deckert, University of Würzburg
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  • Douglas L. Delahanty, Kent State University
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  • Michelle F. Dennis, Duke University, Genetics Research Laboratory
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  • Seth G. Disner, Department of Veterans Affairs
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  • Katharina Domschke, University of Freiburg
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  • Alma Dzubur-Kulenovic, University Clinical Center of Sarajevo
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  • Christopher R. Erbes, Department of Veterans Affairs
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  • Alexandra Evans, Cardiff University
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  • Lindsay A. Farrer, Boston University School of Medicine
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  • Norah C. Feeny, Case Western Reserve University
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  • Janine D. Flory, Icahn School of Medicine at Mount Sinai
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  • David Forbes, University of Melbourne
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  • Carol E. Franz, University of California, San Diego
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  • Sandro Galea, Boston University
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  • Melanie E. Garrett, Duke University
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  • Bizu Gelaye, Harvard School of Public Health
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  • Elbert Geuze, Utrecht, Utrecht University
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  • Charles Gillespie, Emory University
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  • Aferdita Goci Uka, University Clinical Centre of Kosovo
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  • Scott D. Gordon, QIMR Berghofer Medical Research Institute
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  • Guia Guffanti, Harvard University
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  • Rasha Hammamieh, United States Army
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  • Supriya Harnal, Broad Institute
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  • Michael A. Hauser, Duke University
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  • Andrew C. Heath, Internal Medicine, Washington University in St. Louis, School of Medicine
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  • Sian M.J. Hemmings, University of Stellenbosch
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  • David Michael Hougaard, Statens Serum Institut, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
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  • Miro Jakovljevic, School of Medicine and University Hospital Centre, University of Zagreb
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  • Marti Jett, United States Army
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  • Eric Otto Johnson, RTI International
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  • Ian Jones, Cardiff University
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  • Tanja Jovanovic, Emory University
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  • Xue Jun Qin, Duke University
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  • Angela G. Junglen, Kent State University
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  • Karen Inge Karstoft, Research and Knowledge Centre, Københavns Universitet
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  • Milissa L. Kaufman, Harvard University
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  • Ronald C. Kessler, Harvard Medical School
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  • Alaptagin Khan, Harvard Medical School
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  • Nathan A. Kimbrel, Duke University, Genetics Research Laboratory
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  • Anthony P. King, University of Michigan, Ann Arbor
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  • Nastassja Koen, University of Cape Town
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  • Henry R. Kranzler, VA Medical Center
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  • William S. Kremen, VA San Diego Healthcare System
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  • Bruce R. Lawford, Queensland University of Technology
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  • Lauren A.M. Lebois, Harvard University
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  • Catrin E. Lewis, Cardiff University
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  • Sarah D. Linnstaedt, The University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, United States
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  • Adriana Lori, Emory University
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  • Bozo Lugonja, Cardiff University
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  • Jurjen J. Luykx, Utrecht University
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  • Michael J. Lyons, Boston University
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  • Jessica Maples-Keller, Emory University
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  • Charles Marmar, New York University School of Medicine
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  • Alicia R. Martin, Massachusetts General Hospital, Boston
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  • Nicholas G. Martin, QIMR Berghofer Medical Research Institute
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  • Douglas Maurer, United States Army
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  • Matig R. Mavissakalian, University Hospitals Case Medical Center
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  • Alexander McFarlane, University of Adelaide
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  • Regina E. McGlinchey, GRECC/TRACTS
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  • Katie A. McLaughlin, Harvard University
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  • Samuel A. McLean, The University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, United States
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  • Sarah McLeay, Gallipoli Medical Research Institute
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  • Divya Mehta, Queensland University of Technology
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  • William P. Milberg, GRECC/TRACTS
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  • Mark W. Miller, Department of Veterans Affairs
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  • Rajendra A. Morey, Duke University
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  • Charles Phillip Morris, Queensland University of Technology
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  • Ole Mors
  • Preben B. Mortensen
  • Benjamin M. Neale, Massachusetts General Hospital, Boston
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  • Elliot C. Nelson, Internal Medicine, Washington University in St. Louis, School of Medicine
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  • Merete Nordentoft, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Københavns Universitet
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  • Sonya B. Norman, Department of Veterans Affairs
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  • Meaghan O’Donnell, University of Melbourne
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  • Holly K. Orcutt, Northern Illinois University
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  • Matthew S. Panizzon, University of California, San Diego
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  • Edward S. Peters, Louisiana State University Health Sciences Center
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  • Alan L. Peterson, University of Texas Health Science Center at San Antonio
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  • Matthew Peverill, University of Washington, Seattle
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  • Robert H. Pietrzak, Psychiatry
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  • Melissa A. Polusny, Department of Veterans Affairs
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  • John P. Rice, Internal Medicine, Washington University in St. Louis, School of Medicine
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  • Stephan Ripke, Charité – Universitätsmedizin Berlin
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  • Victoria B. Risbrough, VA San Diego Healthcare System
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  • Andrea L. Roberts, Harvard School of Public Health
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  • Alex O. Rothbaum, Case Western Reserve University
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  • Barbara O. Rothbaum, Emory University
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  • Peter Roy-Byrne, University of Washington, Seattle
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  • Ken Ruggiero, Medical University of South Carolina
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  • Ariane Rung, Louisiana State University Health Sciences Center
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  • Bart P.F. Rutten, University Medical Centre Maastricht
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  • Nancy L. Saccone, Internal Medicine, Washington University in St. Louis, School of Medicine
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  • Sixto E. Sanchez, Universidad Peruana de Ciencias Aplicadas Facultad de Ciencias de la Salud
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  • Dick Schijven, Utrecht University
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  • Soraya Seedat, University of Stellenbosch
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  • Antonia V. Seligowski, Harvard University
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  • Julia S. Seng, University of Michigan, Ann Arbor, Michigan.
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  • Christina M. Sheerin, Virginia Commonwealth University
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  • Derrick Silove, University of New South Wales (UNSW) Australia
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  • Alicia K. Smith, Emory University
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  • Jordan W. Smoller, Massachusetts General Hospital, Boston
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  • Scott R. Sponheim, University of Minnesota
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  • Dan J. Stein, University of Cape Town
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  • Jennifer S. Stevens, Emory University
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  • Jennifer A. Sumner, Columbia University
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  • Martin H. Teicher, Harvard University
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  • Wesley K. Thompson, University of California, San Diego, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Institute of Biological Psychiatry, University of Oslo, Oslo University Hospital, Oslo
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  • Edward Trapido, Louisiana State University Health Sciences Center
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  • Monica Uddin, University of South Florida
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  • Robert J. Ursano, Uniformed Services University of the Health Sciences
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  • Leigh Luella van den Heuvel, University of Stellenbosch
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  • Miranda Van Hooff, University of Adelaide
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  • Eric Vermetten, New York University School of Medicine, Arq, Department of Human Genetics, Leiden University Medical Center (LUMC)., Research Center
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  • Christiaan H. Vinkers, Vrije Universiteit Amsterdam
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  • Joanne Voisey, Queensland University of Technology
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  • Yunpeng Wang, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Institute of Biological Psychiatry, University of Oslo, Oslo University Hospital, Oslo
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  • Zhewu Wang, Medical University of South Carolina
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  • Thomas Werge, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Institute of Biological Psychiatry, Københavns Universitet
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  • Michelle A. Williams, Harvard School of Public Health
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  • Douglas E. Williamson, Duke University
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  • Sherry Winternitz, Harvard University
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  • Christiane Wolf, University of Würzburg
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  • Erika J. Wolf, Department of Veterans Affairs
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  • Jonathan D. Wolff, Harvard University
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  • Rachel Yehuda, VA Medical Center
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  • Ross Mc D. Young, Queensland University of Technology
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  • Keith A. Young, Scott and White Memorial Hospital, COE for Research on Returning War Veterans
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  • Hongyu Zhao, Yale University
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  • Lori A. Zoellner, University of Washington, Seattle
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  • Israel Liberzon, University of Michigan, Ann Arbor
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  • Kerry J. Ressler, Emory University
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  • Magali Haas, Cohen Veterans Bioscience
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  • Karestan C. Koenen, Harvard School of Public Health

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

Original languageEnglish
Article number4558
JournalNature Communications
Volume10
Issue1
ISSN2041-1723
DOIs
Publication statusPublished - Dec 2019

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