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

Author

Listed:
  • Caroline M. Nievergelt

    (University of California San Diego, Department of Psychiatry
    Center of Excellence for Stress and Mental Health
    Research Service)

  • Adam X. Maihofer

    (University of California San Diego, Department of Psychiatry
    Center of Excellence for Stress and Mental Health
    Research Service)

  • Torsten Klengel

    (Harvard Medical School, Department of Psychiatry
    McLean Hospital
    University Medical Center Goettingen, Department of Psychiatry)

  • Elizabeth G. Atkinson

    (Stanley Center for Psychiatric Research
    Analytic and Translational Genetics Unit)

  • Chia-Yen Chen

    (Stanley Center for Psychiatric Research
    Analytic and Translational Genetics Unit
    Psychiatric and Neurodevelopmental Genetics Unit (PNGU))

  • Karmel W. Choi

    (Stanley Center for Psychiatric Research
    Massachusetts General Hospital, Department of Psychiatry
    Harvard T.H. Chan School of Public Health, Department of Epidemiology)

  • Jonathan R. I. Coleman

    (Institute of Psychiatry, Psychology and Neuroscience
    King’s College London, NIHR BRC at the Maudsley)

  • Shareefa Dalvie

    (University of Cape Town, SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Cape Town)

  • Laramie E. Duncan

    (Stanford University, Department of Psychiatry and Behavioral Sciences)

  • Joel Gelernter

    (US Department of Veterans Affairs, Department of Psychiatry
    Yale University School of Medicine, Department of Genetics and Neuroscience
    VA Connecticut Healthcare Center)

  • Daniel F. Levey

    (VA Connecticut Healthcare Center
    Yale University School of Medicine, Department of Psychiatry)

  • Mark W. Logue

    (National Center for PTSD)

  • Renato Polimanti

    (VA Connecticut Healthcare Center
    Yale University School of Medicine, Department of Psychiatry)

  • Allison C. Provost

    (Cohen Veterans Bioscience)

  • Andrew Ratanatharathorn

    (Harvard T.H. Chan School of Public Health, Department of Epidemiology)

  • Murray B. Stein

    (University of California San Diego, Department of Psychiatry
    Million Veteran Program
    Psychiatry Service)

  • Katy Torres

    (University of California San Diego, Department of Psychiatry
    Center of Excellence for Stress and Mental Health
    Research Service)

  • Allison E. Aiello

    (Department of Epidemiology)

  • Lynn M. Almli

    (Emory University, Department of Psychiatry and Behavioral Sciences)

  • Ananda B. Amstadter

    (Department of Psychiatry)

  • Søren B. Andersen

    (Research and Knowledge Centre)

  • Ole A. Andreassen

    (University of Oslo, Institute of Clinical Medicine)

  • Paul A. Arbisi

    (Mental Health Service Line)

  • Allison E. Ashley-Koch

    (Duke University, Duke Molecular Physiology Institute)

  • S. Bryn Austin

    (Harvard Medical School, Department of Psychiatry
    Division of Adolescent and Young Adult Medicine
    Channing Division of Network Medicine
    Department of Social and Behavioral Sciences)

  • Esmina Avdibegovic

    (University Clinical Center of Tuzla, Department of Psychiatry)

  • Dragan Babić

    (University Clinical Center of Mostar, Department of Psychiatry)

  • Marie Bækvad-Hansen

    (Statens Serum Institut, Department for Congenital Disorders
    The Lundbeck Foundation Initiative for Integrative Psychiatric Research)

  • Dewleen G. Baker

    (University of California San Diego, Department of Psychiatry
    Center of Excellence for Stress and Mental Health
    Psychiatry Service)

  • Jean C. Beckham

    (Durham VA Medical Center, Research
    Duke University, Department of Psychiatry and Behavioral Sciences
    Education, and Clinical Center (MIRECC), Genetics Research Laboratory)

  • Laura J. Bierut

    (Washington University in Saint Louis School of Medicine, Department of Psychiatry)

  • Jonathan I. Bisson

    (Cardiff University, National Centre for Mental Health, MRC Centre for Psychiatric Genetics and Genomics)

  • Marco P. Boks

    (UMC Utrecht Brain Center Rudolf Magnus, Department of Translational Neuroscience, Utrecht)

  • Elizabeth A. Bolger

    (Harvard Medical School, Department of Psychiatry
    McLean Hospital)

  • Anders D. Børglum

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Aarhus University, Centre for Integrative Sequencing, iSEQ
    Aarhus University, Department of Biomedicine - Human Genetics)

  • Bekh Bradley

    (Emory University, Department of Psychiatry and Behavioral Sciences
    Mental Health Service Line)

  • Megan Brashear

    (Louisiana State University Health Sciences Center, School of Public Health and Department of Epidemiology)

  • Gerome Breen

    (Institute of Psychiatry, Psychology and Neuroscience
    King’s College London, NIHR BRC at the Maudsley)

  • Richard A. Bryant

    (University of New South Wales, Department of Psychology)

  • Angela C. Bustamante

    (University of Michigan Medical School, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine)

  • Jonas Bybjerg-Grauholm

    (Statens Serum Institut, Department for Congenital Disorders
    The Lundbeck Foundation Initiative for Integrative Psychiatric Research)

  • Joseph R. Calabrese

    (University Hospitals, Department of Psychiatry)

  • José M. Caldas- de- Almeida

    (Lisbon Institute of Global Mental Health)

  • Anders M. Dale

    (University of California San Diego, Department of Radiology, Department of Neurosciences)

  • Mark J. Daly

    (Psychiatric and Neurodevelopmental Genetics Unit (PNGU))

  • Nikolaos P. Daskalakis

    (Harvard Medical School, Department of Psychiatry
    McLean Hospital
    Cohen Veterans Bioscience
    Icahn School of Medicine at Mount Sinai, Department of Psychiatry)

  • Jürgen Deckert

    (University Hospital of Würzburg, Center of Mental Health, Psychiatry, Psychosomatics and Psychotherapy)

  • Douglas L. Delahanty

    (Kent State University, Department of Psychological Sciences
    Kent State University, Research and Sponsored Programs)

  • Michelle F. Dennis

    (Durham VA Medical Center, Research
    Duke University, Department of Psychiatry and Behavioral Sciences
    Education, and Clinical Center (MIRECC), Genetics Research Laboratory)

  • Seth G. Disner

    (Research Service Line)

  • Katharina Domschke

    (Department of Psychiatry and Psychotherapy
    University of Freiburg, Faculty of Medicine, Centre for Basics in Neuromodulation)

  • Alma Dzubur-Kulenovic

    (University Clinical Center of Sarajevo, Department of Psychiatry)

  • Christopher R. Erbes

    (University of Minnesota, Department of Psychiatry
    Center for Care Delivery and Outcomes Research (CCDOR))

  • Alexandra Evans

    (Cardiff University, National Centre for Mental Health, MRC Centre for Psychiatric Genetics and Genomics, Cardiff)

  • Lindsay A. Farrer

    (Boston University School of Medicine, Department of Medicine)

  • Norah C. Feeny

    (Case Western Reserve University, Department of Psychological Sciences)

  • Janine D. Flory

    (Icahn School of Medicine at Mount Sinai, Department of Psychiatry)

  • David Forbes

    (University of Melbourne, Department of Psychiatry, Melbourne)

  • Carol E. Franz

    (University of California San Diego, Department of Psychiatry)

  • Sandro Galea

    (Boston University, Department of Psychological and Brain Sciences)

  • Melanie E. Garrett

    (Duke University, Department of Psychiatry and Behavioral Sciences)

  • Bizu Gelaye

    (Harvard T.H. Chan School of Public Health, Department of Epidemiology)

  • Elbert Geuze

    (Brain Research and Innovation Centre, Utrecht
    Department of Psychiatry, Utrecht)

  • Charles Gillespie

    (Emory University, Department of Psychiatry and Behavioral Sciences)

  • Aferdita Goci Uka

    (University Clinical Centre of Kosovo, Department of Psychiatry, Prishtina)

  • Scott D. Gordon

    (Department of Genetics and Computational Biology)

  • Guia Guffanti

    (Harvard Medical School, Department of Psychiatry
    McLean Hospital)

  • Rasha Hammamieh

    (USACEHR)

  • Supriya Harnal

    (Stanley Center for Psychiatric Research)

  • Michael A. Hauser

    (Duke University, Department of Psychiatry and Behavioral Sciences)

  • Andrew C. Heath

    (Washington University in Saint Louis School of Medicine, Department of Genetics)

  • Sian M. J. Hemmings

    (Stellenbosch University Faculty of Medicine and Health Sciences, Department of Psychiatry, Cape Town)

  • David Michael Hougaard

    (Statens Serum Institut, Department for Congenital Disorders
    The Lundbeck Foundation Initiative for Integrative Psychiatric Research)

  • Miro Jakovljevic

    (University Hospital Center of Zagreb, Department of Psychiatry)

  • Marti Jett

    (USACEHR)

  • Eric Otto Johnson

    (RTI International, Behavioral Health and Criminal Justice Division)

  • Ian Jones

    (Cardiff University, National Centre for Mental Health, MRC Centre for Psychiatric Genetics and Genomics, Cardiff)

  • Tanja Jovanovic

    (Emory University, Department of Psychiatry and Behavioral Sciences)

  • Xue-Jun Qin

    (Duke University, Duke Molecular Physiology Institute)

  • Angela G. Junglen

    (Kent State University, Department of Psychological Sciences)

  • Karen-Inge Karstoft

    (Research and Knowledge Centre
    University of Copenhagen, Department of Psychology)

  • Milissa L. Kaufman

    (Harvard Medical School, Department of Psychiatry
    McLean Hospital)

  • Ronald C. Kessler

    (Harvard Medical School, Department of Psychiatry)

  • Alaptagin Khan

    (McLean Hospital
    Department of Health Care Policy)

  • Nathan A. Kimbrel

    (Duke University, Duke Molecular Physiology Institute
    Durham VA Medical Center, Research
    Education, and Clinical Center (MIRECC), Genetics Research Laboratory)

  • Anthony P. King

    (University of Michigan Medical School, Department of Psychiatry)

  • Nastassja Koen

    (University of Cape Town, SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Cape Town)

  • Henry R. Kranzler

    (University of Pennsylvania Perelman School of Medicine, Department of Psychiatry
    Mental Illness Research, Education and Clinical Center, Crescenz VAMC)

  • William S. Kremen

    (University of California San Diego, Department of Psychiatry
    Center of Excellence for Stress and Mental Health)

  • Bruce R. Lawford

    (Queensland University of Technology, Institute of Health and Biomedical Innovation, Kelvin Grove
    Queensland University of Technology, School of Biomedical Sciences, Kelvin Grove)

  • Lauren A. M. Lebois

    (Harvard Medical School, Department of Psychiatry
    McLean Hospital)

  • Catrin E. Lewis

    (Cardiff University, National Centre for Mental Health, MRC Centre for Psychiatric Genetics and Genomics, Cardiff)

  • Sarah D. Linnstaedt

    (Department of Anesthesiology)

  • Adriana Lori

    (Emory University, Department of Gynecology and Obstetrics)

  • Bozo Lugonja

    (Cardiff University, National Centre for Mental Health, MRC Centre for Psychiatric Genetics and Genomics, Cardiff)

  • Jurjen J. Luykx

    (UMC Utrecht Brain Center Rudolf Magnus, Department of Translational Neuroscience, Utrecht
    Department of Psychiatry, Utrecht)

  • Michael J. Lyons

    (Boston University, Dean’s Office)

  • Jessica Maples-Keller

    (Emory University, Department of Psychiatry and Behavioral Sciences)

  • Charles Marmar

    (New York University School of Medicine, Department of Psychiatry)

  • Alicia R. Martin

    (Stanley Center for Psychiatric Research
    Analytic and Translational Genetics Unit)

  • Nicholas G. Martin

    (Department of Genetics and Computational Biology)

  • Douglas Maurer

    (United States Army, Command)

  • Matig R. Mavissakalian

    (University Hospitals, Department of Psychiatry)

  • Alexander McFarlane

    (University of Adelaide, Department of Psychiatry, Adelaide)

  • Regina E. McGlinchey

    (VA Boston Health Care System, GRECC/TRACTS)

  • Katie A. McLaughlin

    (Harvard University, Department of Psychology)

  • Samuel A. McLean

    (Department of Anesthesiology
    Department of Emergency Medicine)

  • Sarah McLeay

    (Gallipoli Medical Research Institute, PTSD Initiative, Greenslopes)

  • Divya Mehta

    (Queensland University of Technology, Institute of Health and Biomedical Innovation, Kelvin Grove
    Queensland University of Technology, School of Psychology and Counseling, Faculty of Health, Kelvin Grove)

  • William P. Milberg

    (VA Boston Health Care System, GRECC/TRACTS)

  • Mark W. Miller

    (National Center for PTSD)

  • Rajendra A. Morey

    (Duke University, Duke Molecular Physiology Institute)

  • Charles Phillip Morris

    (Queensland University of Technology, Institute of Health and Biomedical Innovation, Kelvin Grove
    Queensland University of Technology, School of Biomedical Sciences, Kelvin Grove)

  • Ole Mors

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Aarhus University Hospital, Psychosis Research Unit)

  • Preben B. Mortensen

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Aarhus University, Centre for Integrative Sequencing, iSEQ
    Aarhus University, Centre for Integrated Register-based Research
    Aarhus University, National Centre for Register-Based Research)

  • Benjamin M. Neale

    (Stanley Center for Psychiatric Research
    Analytic and Translational Genetics Unit)

  • Elliot C. Nelson

    (Washington University in Saint Louis School of Medicine, Department of Psychiatry)

  • Merete Nordentoft

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    University of Copenhagen, Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen)

  • Sonya B. Norman

    (University of California San Diego, Department of Psychiatry
    Department of Research and Psychiatry
    National Center for Post Traumatic Stress Disorder, Executive Division, White River Junction)

  • Meaghan O’Donnell

    (University of Melbourne, Department of Psychiatry, Melbourne)

  • Holly K. Orcutt

    (Northern Illinois University, Department of Psychology)

  • Matthew S. Panizzon

    (University of California San Diego, Department of Psychiatry)

  • Edward S. Peters

    (Louisiana State University Health Sciences Center, School of Public Health and Department of Epidemiology)

  • Alan L. Peterson

    (University of Texas Health Science Center at San Antonio, Department of Psychiatry)

  • Matthew Peverill

    (University of Washington, Department of Psychology)

  • Robert H. Pietrzak

    (Yale University School of Medicine, Department of Psychiatry
    U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder)

  • Melissa A. Polusny

    (University of Minnesota, Department of Psychiatry
    Department of Mental Health
    Department of Psychology)

  • John P. Rice

    (Washington University in Saint Louis School of Medicine, Department of Psychiatry)

  • Stephan Ripke

    (Stanley Center for Psychiatric Research
    Psychiatric and Neurodevelopmental Genetics Unit (PNGU)
    Charité - Universitätsmedizin, Department of Psychiatry and Psychotherapy)

  • Victoria B. Risbrough

    (University of California San Diego, Department of Psychiatry
    Center of Excellence for Stress and Mental Health
    Research Service)

  • Andrea L. Roberts

    (Department of Environmental Health)

  • Alex O. Rothbaum

    (Case Western Reserve University, Department of Psychological Sciences)

  • Barbara O. Rothbaum

    (Emory University, Department of Psychiatry and Behavioral Sciences)

  • Peter Roy-Byrne

    (University of Washington, Department of Psychology)

  • Ken Ruggiero

    (Medical University of South Carolina, Department of Nursing and Department of Psychiatry)

  • Ariane Rung

    (Louisiana State University Health Sciences Center, School of Public Health and Department of Epidemiology)

  • Bart P. F. Rutten

    (Maastricht Universitair Medisch Centrum, School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht)

  • Nancy L. Saccone

    (Washington University in Saint Louis School of Medicine, Department of Psychiatry)

  • Sixto E. Sanchez

    (Universidad Peruana de Ciencias Aplicadas Facultad de Ciencias de la Salud, Department of Medicine, Lima)

  • Dick Schijven

    (UMC Utrecht Brain Center Rudolf Magnus, Department of Translational Neuroscience, Utrecht
    Department of Psychiatry, Utrecht)

  • Soraya Seedat

    (Stellenbosch University Faculty of Medicine and Health Sciences, Department of Psychiatry, Cape Town)

  • Antonia V. Seligowski

    (Harvard Medical School, Department of Psychiatry
    McLean Hospital)

  • Julia S. Seng

    (University of Michigan, School of Nursing)

  • Christina M. Sheerin

    (Department of Psychiatry)

  • Derrick Silove

    (University of New South Wales, Department of Psychiatry, Sydney)

  • Alicia K. Smith

    (Emory University, Department of Psychiatry and Behavioral Sciences
    Emory University, Department of Gynecology and Obstetrics)

  • Jordan W. Smoller

    (Stanley Center for Psychiatric Research
    Analytic and Translational Genetics Unit
    Massachusetts General Hospital, Department of Psychiatry)

  • Scott R. Sponheim

    (Mental Health Service Line
    University of Minnesota, Department of Psychiatry)

  • Dan J. Stein

    (University of Cape Town, SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Cape Town)

  • Jennifer S. Stevens

    (Emory University, Department of Psychiatry and Behavioral Sciences)

  • Jennifer A. Sumner

    (Columbia University Medical Center, Department of Medicine)

  • Martin H. Teicher

    (Harvard Medical School, Department of Psychiatry
    McLean Hospital)

  • Wesley K. Thompson

    (University of California San Diego, Department of Psychiatry
    The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Institute of Biological Psychiatry
    Oslo University Hospital, KG Jebsen Centre for Psychosis Research, Norway Division of Mental Health and Addiction)

  • Edward Trapido

    (Louisiana State University Health Sciences Center, School of Public Health and Department of Epidemiology)

  • Monica Uddin

    (University of South Florida College of Public Health, Genomics Program)

  • Robert J. Ursano

    (Uniformed Services University, Department of Psychiatry)

  • Leigh Luella Heuvel

    (Stellenbosch University Faculty of Medicine and Health Sciences, Department of Psychiatry, Cape Town)

  • Miranda Hooff

    (University of Adelaide, Department of Psychiatry, Adelaide)

  • Eric Vermetten

    (New York University School of Medicine, Department of Psychiatry
    Arq, Psychotrauma Reseach Expert Group
    Leiden University Medical Center, Department of Psychiatry
    Research Center)

  • Christiaan H. Vinkers

    (Department of Anatomy and Neurosciences, Amsterdam
    Amsterdam UMC (location VUmc), Department of Psychiatry, Amsterdam)

  • Joanne Voisey

    (Queensland University of Technology, Institute of Health and Biomedical Innovation, Kelvin Grove
    Queensland University of Technology, School of Biomedical Sciences, Kelvin Grove)

  • Yunpeng Wang

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Institute of Biological Psychiatry
    Oslo University Hospital, KG Jebsen Centre for Psychosis Research, Norway Division of Mental Health and Addiction)

  • Zhewu Wang

    (Department of Mental Health
    Department of Psychiatry and Behavioral Sciences)

  • Thomas Werge

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Institute of Biological Psychiatry
    University of Copenhagen, Department of Clinical Medicine)

  • Michelle A. Williams

    (Harvard T.H. Chan School of Public Health, Department of Epidemiology)

  • Douglas E. Williamson

    (Durham VA Medical Center, Research
    Duke University, Department of Psychiatry and Behavioral Sciences)

  • Sherry Winternitz

    (Harvard Medical School, Department of Psychiatry
    McLean Hospital)

  • Christiane Wolf

    (University Hospital of Würzburg, Center of Mental Health, Psychiatry, Psychosomatics and Psychotherapy)

  • Erika J. Wolf

    (National Center for PTSD)

  • Jonathan D. Wolff

    (McLean Hospital)

  • Rachel Yehuda

    (Icahn School of Medicine at Mount Sinai, Department of Psychiatry
    Department of Mental Health)

  • Ross McD. Young

    (Queensland University of Technology, Institute of Health and Biomedical Innovation, Kelvin Grove
    Queensland University of Technology, School of Psychology and Counseling, Faculty of Health, Kelvin Grove)

  • Keith A. Young

    (Department of Psychiatry
    CTVHCS, COE for Research on Returning War Veterans)

  • Hongyu Zhao

    (Yale University, Department of Biostatistics)

  • Lori A. Zoellner

    (University of Washington, Department of Psychiatry and Behavioral Sciences)

  • Israel Liberzon

    (University of Michigan Medical School, Department of Psychiatry)

  • Kerry J. Ressler

    (Harvard Medical School, Department of Psychiatry
    McLean Hospital
    Emory University, Department of Psychiatry and Behavioral Sciences)

  • Magali Haas

    (Cohen Veterans Bioscience)

  • Karestan C. Koenen

    (Stanley Center for Psychiatric Research
    Psychiatric and Neurodevelopmental Genetics Unit (PNGU)
    Department of Epidemiology)

Abstract

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.

Suggested Citation

  • Caroline M. Nievergelt & Adam X. Maihofer & Torsten Klengel & Elizabeth G. Atkinson & Chia-Yen Chen & Karmel W. Choi & Jonathan R. I. Coleman & Shareefa Dalvie & Laramie E. Duncan & Joel Gelernter & D, 2019. "International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12576-w
    DOI: 10.1038/s41467-019-12576-w
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    Cited by:

    1. Royce E. Clifford & Adam X. Maihofer & Chris Chatzinakos & Jonathan R. I. Coleman & Nikolaos P. Daskalakis & Marianna Gasperi & Kelleigh Hogan & Elizabeth A. Mikita & Murray B. Stein & Catherine Tchea, 2024. "Genetic architecture distinguishes tinnitus from hearing loss," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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