International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.
Journal: Nature communications
Volume: 10
Issue: 1
Year of Publication: 2020
Affiliated Institutions: University of California San Diego, Department of Psychiatry, La Jolla, CA, USA. cnievergelt@ucsd.edu. University of California San Diego, Department of Psychiatry, La Jolla, CA, USA. Harvard Medical School, Department of Psychiatry, Boston, MA, USA. Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA. King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, London, GB, USA. University of Cape Town, SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Cape Town, Western Cape, ZA, USA. Stanford University, Department of Psychiatry and Behavioral Sciences, Stanford, CA, USA. US Department of Veterans Affairs, Department of Psychiatry, West Haven, CT, USA. VA Connecticut Healthcare Center, West Haven, CT, USA. VA Boston Healthcare System, National Center for PTSD, Boston, MA, USA. Cohen Veterans Bioscience, Cambridge, MA, USA. Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, MA, USA. Gillings School of Global Public Health, Department of Epidemiology, Chapel Hill, NC, USA. Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA. Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Richmond, VA, USA. The Danish Veteran Centre, Research and Knowledge Centre, Ringsted, Sjaelland, Denmark. University of Oslo, Institute of Clinical Medicine, Oslo, NO, Norway. Minneapolis VA Health Care System, Mental Health Service Line, Minneapolis, MN, USA. Duke University, Duke Molecular Physiology Institute, Durham, NC, USA. University Clinical Center of Tuzla, Department of Psychiatry, Tuzla, BA, Bosnia and Herzegovina. University Clinical Center of Mostar, Department of Psychiatry, Mostar, BA, Bosnia and Herzegovina. Statens Serum Institut, Department for Congenital Disorders, Copenhagen, DK, Denmark. Durham VA Medical Center, Research, Durham, NC, USA. Washington University in Saint Louis School of Medicine, Department of Psychiatry, Saint Louis, MO, USA. Cardiff University, National Centre for Mental Health, MRC Centre for Psychiatric Genetics and Genomics, Cardiff, UK. UMC Utrecht Brain Center Rudolf Magnus, Department of Translational Neuroscience, Utrecht, Utrecht, NL, Netherlands. The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, DK, Denmark. Louisiana State University Health Sciences Center, School of Public Health and Department of Epidemiology, New Orleans, LA, USA. University of New South Wales, Department of Psychology, Sydney, NSW, Australia. University of Michigan Medical School, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ann Arbor, MI, USA. University Hospitals, Department of Psychiatry, Cleveland, OH, USA. CEDOC -Chronic Diseases Research Centre, Lisbon Institute of Global Mental Health, Lisbon, PT, Portugal. University of California San Diego, Department of Radiology, Department of Neurosciences, La Jolla, CA, USA. Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Boston, MA, USA. University Hospital of Würzburg, Center of Mental Health, Psychiatry, Psychosomatics and Psychotherapy, Würzburg, DE, Germany. Kent State University, Department of Psychological Sciences, Kent, OH, USA. Minneapolis VA Health Care System, Research Service Line, Minneapolis, MN, USA. Medical Center-University of Freiburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Freiburg, DE, Germany. University Clinical Center of Sarajevo, Department of Psychiatry, Sarajevo, BA, Bosnia and Herzegovina. University of Minnesota, Department of Psychiatry, Minneapolis, MN, USA. Cardiff University, National Centre for Mental Health, MRC Centre for Psychiatric Genetics and Genomics, Cardiff, South Glamorgan, GB, USA. Boston University School of Medicine, Department of Medicine, Boston, MA, USA. Case Western Reserve University, Department of Psychological Sciences, Cleveland, OH, USA. Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, NY, USA. University of Melbourne, Department of Psychiatry, Melbourne, VIC, AU, USA. Boston University, Department of Psychological and Brain Sciences, Boston, MA, USA. Duke University, Department of Psychiatry and Behavioral Sciences, Durham, NC, USA. Netherlands Ministry of Defence, Brain Research and Innovation Centre, Utrecht, Utrecht, NL, Netherlands. University Clinical Centre of Kosovo, Department of Psychiatry, Prishtina, Kosovo, XK, USA. QIMR Berghofer Medical Research Institute, Department of Genetics and Computational Biology, Brisbane, Queensland, Australia. US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, MD, USA. Washington University in Saint Louis School of Medicine, Department of Genetics, Saint Louis, MO, USA. Stellenbosch University Faculty of Medicine and Health Sciences, Department of Psychiatry, Cape Town, Western Cape, ZA, South Africa. University Hospital Center of Zagreb, Department of Psychiatry, Zagreb, HR, USA. RTI International, Behavioral Health and Criminal Justice Division, Research Triangle Park, NC, USA. McLean Hospital, Belmont, MA, USA. University of Michigan Medical School, Department of Psychiatry, Ann Arbor, MI, USA. University of Pennsylvania Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA. Queensland University of Technology, Institute of Health and Biomedical Innovation, Kelvin Grove, QLD, AU, Australia. UNC Institute for Trauma Recovery, Department of Anesthesiology, Chapel Hill, NC, USA. Emory University, Department of Gynecology and Obstetrics, Atlanta, GA, USA. Boston University, Dean's Office, Boston, MA, USA. New York University School of Medicine, Department of Psychiatry, New York, NY, USA. United States Army, Command, Fort Sill, OK, USA. University of Adelaide, Department of Psychiatry, Adelaide, South Australia, AU, Australia. VA Boston Health Care System, GRECC/TRACTS, Boston, MA, USA. Harvard University, Department of Psychology, Boston, MA, USA. Gallipoli Medical Research Institute, PTSD Initiative, Greenslopes, Queensland, AU, Australia. Northern Illinois University, Department of Psychology, DeKalb, IL, USA. University of Texas Health Science Center at San Antonio, Department of Psychiatry, San Antonio, TX, USA. University of Washington, Department of Psychology, Seattle, WA, USA. Yale University School of Medicine, Department of Psychiatry, New Haven, CT, USA. Harvard T.H. Chan School of Public Health, Department of Environmental Health, Boston, MA, USA. Medical University of South Carolina, Department of Nursing and Department of Psychiatry, Charleston, SC, USA. Maastricht Universitair Medisch Centrum, School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht, Limburg, NL, Netherlands. Universidad Peruana de Ciencias Aplicadas Facultad de Ciencias de la Salud, Department of Medicine, Lima, Lima, PE, USA. University of Michigan, School of Nursing, Ann Arbor, MI, USA. University of New South Wales, Department of Psychiatry, Sydney, NSW, AU, USA. Columbia University Medical Center, Department of Medicine, New York, NY, USA. University of South Florida College of Public Health, Genomics Program, Tampa, FL, USA. Uniformed Services University, Department of Psychiatry, Bethesda, Maryland, USA. Amsterdam UMC (location VUmc), Department of Anatomy and Neurosciences, Amsterdam, Holland, NL, Netherlands. Ralph H Johnson VA Medical Center, Department of Mental Health, Charleston, SC, USA. Baylor Scott and White Central Texas, Department of Psychiatry, Temple, TX, USA. Yale University, Department of Biostatistics, New Haven, CT, USA. University of Washington, Department of Psychiatry and Behavioral Sciences, Seattle, WA, USA.
Abstract summary
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.Authors & Co-authors: Nievergelt Caroline M CM Maihofer Adam X AX Klengel Torsten T Atkinson Elizabeth G EG Chen Chia-Yen CY Choi Karmel W KW Coleman Jonathan R I JRI Dalvie Shareefa S Duncan Laramie E LE Gelernter Joel J Levey Daniel F DF Logue Mark W MW Polimanti Renato R Provost Allison C AC Ratanatharathorn Andrew A Stein Murray B MB Torres Katy K Aiello Allison E AE Almli Lynn M LM Amstadter Ananda B AB Andersen Søren B SB Andreassen Ole A OA Arbisi Paul A PA Ashley-Koch Allison E AE Austin S Bryn SB Avdibegovic Esmina E Babić Dragan D Bækvad-Hansen Marie M Baker Dewleen G DG Beckham Jean C JC Bierut Laura J LJ Bisson Jonathan I JI Boks Marco P MP Bolger Elizabeth A EA Børglum Anders D AD Bradley Bekh B Brashear Megan M Breen Gerome G Bryant Richard A RA Bustamante Angela C AC Bybjerg-Grauholm Jonas J Calabrese Joseph R JR Caldas-de-Almeida José M JM Dale Anders M AM Daly Mark J MJ Daskalakis Nikolaos P NP Deckert Jürgen J Delahanty Douglas L DL Dennis Michelle F MF Disner Seth G SG Domschke Katharina K Dzubur-Kulenovic Alma A Erbes Christopher R CR Evans Alexandra A Farrer Lindsay A LA Feeny Norah C NC Flory Janine D JD Forbes David D Franz Carol E CE Galea Sandro S Garrett Melanie E ME Gelaye Bizu B Geuze Elbert E Gillespie Charles C Uka Aferdita Goci AG Gordon Scott D SD Guffanti Guia G Hammamieh Rasha R Harnal Supriya S Hauser Michael A MA Heath Andrew C AC Hemmings Sian M J SMJ Hougaard David Michael DM Jakovljevic Miro M Jett Marti M Johnson Eric Otto EO Jones Ian I Jovanovic Tanja T Qin Xue-Jun XJ Junglen Angela G AG Karstoft Karen-Inge KI Kaufman Milissa L ML Kessler Ronald C RC Khan Alaptagin A Kimbrel Nathan A NA King Anthony P AP Koen Nastassja N Kranzler Henry R HR Kremen William S WS Lawford Bruce R BR Lebois Lauren A M LAM Lewis Catrin E CE Linnstaedt Sarah D SD Lori Adriana A Lugonja Bozo B Luykx Jurjen J JJ Lyons Michael J MJ Maples-Keller Jessica J Marmar Charles C Martin Alicia R AR Martin Nicholas G NG Maurer Douglas D Mavissakalian Matig R MR McFarlane Alexander A McGlinchey Regina E RE McLaughlin Katie A KA McLean Samuel A SA McLeay Sarah S Mehta Divya D Milberg William P WP Miller Mark W MW Morey Rajendra A RA Morris Charles Phillip CP Mors Ole O Mortensen Preben B PB Neale Benjamin M BM Nelson Elliot C EC Nordentoft Merete M Norman Sonya B SB O'Donnell Meaghan M Orcutt Holly K HK Panizzon Matthew S MS Peters Edward S ES Peterson Alan L AL Peverill Matthew M Pietrzak Robert H RH Polusny Melissa A MA Rice John P JP Ripke Stephan S Risbrough Victoria B VB Roberts Andrea L AL Rothbaum Alex O AO Rothbaum Barbara O BO Roy-Byrne Peter P Ruggiero Ken K Rung Ariane A Rutten Bart P F BPF Saccone Nancy L NL Sanchez Sixto E SE Schijven Dick D Seedat Soraya S Seligowski Antonia V AV Seng Julia S JS Sheerin Christina M CM Silove Derrick D Smith Alicia K AK Smoller Jordan W JW Sponheim Scott R SR Stein Dan J DJ Stevens Jennifer S JS Sumner Jennifer A JA Teicher Martin H MH Thompson Wesley K WK Trapido Edward E Uddin Monica M Ursano Robert J RJ van den Heuvel Leigh Luella LL Van Hooff Miranda M Vermetten Eric E Vinkers Christiaan H CH Voisey Joanne J Wang Yunpeng Y Wang Zhewu Z Werge Thomas T Williams Michelle A MA Williamson Douglas E DE Winternitz Sherry S Wolf Christiane C Wolf Erika J EJ Wolff Jonathan D JD Yehuda Rachel R Young Ross McD RM Young Keith A KA Zhao Hongyu H Zoellner Lori A LA Liberzon Israel I Ressler Kerry J KJ Haas Magali M Koenen Karestan C KC
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Citations : Ben Barnes J, Hayes AM, Contractor AA, Nash WP, Litz BT. The structure of co-occurring PTSD and depression symptoms in a cohort of Marines pre- and post-deployment. Psychiatry Res. 2018;259:442–449. doi: 10.1016/j.psychres.2017.10.045.Authors : 179
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Doi : 4558SSN : 2041-1723