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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
neuroscience
Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information
Biological Psychiatry, Volume 91, No. 7, Year 2022
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Description
Background: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods. © 2021 Society of Biological Psychiatry
Authors & Co-Authors
Maihofer, Adam X.
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Choi, Karmel W.
United States, Boston
Harvard T.h. Chan School of Public Health
United States, Boston
Massachusetts General Hospital
Coleman, Jonathan R.I.
United Kingdom, London
King's College London
Daskalakis, Nikolaos P.
United States, Boston
Harvard Medical School
United States, Cambridge
Massachusetts Institute of Technology
Denckla, Christy A.
United States, Boston
Harvard T.h. Chan School of Public Health
United States, Cambridge
Massachusetts Institute of Technology
Ketema, Elizabeth
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Morey, Rajendra A.
United States, Durham
Duke University
Polimanti, Renato
United States, West Haven
Va Connecticut Healthcare System
United States, New Haven
Yale School of Medicine
Ratanatharathorn, Andrew D.
United States, Boston
Harvard T.h. Chan School of Public Health
United States, New York
Mailman School of Public Health
Torres, Katy
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Wingo, Aliza P.
United States, Decatur
Atlanta va Medical Center
United States, Atlanta
Emory University School of Medicine
Zai, Clement C.
United States, Boston
Harvard T.h. Chan School of Public Health
United States, Cambridge
Massachusetts Institute of Technology
Canada, Toronto
Centre for Addiction and Mental Health
Canada, Toronto
University of Toronto
Aiello, Allison E.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Almli, Lynn M.
United States, Atlanta
Emory University School of Medicine
Amstadter, Ananda Beth
United States, Richmond
Virginia Institute for Psychiatric and Behavioral Genetics
Andersen, Søren Bo
Unknown Affiliation
Andreassen, Ole Andreas
Norway, Oslo
Oslo Universitetssykehus
Norway, Oslo
Universitetet I Oslo
Arbisi, Paul A.
United States, Minneapolis
University of Minnesota Twin Cities
Ashley-Koch, Allison E.
United States, Durham
Duke University
Austin, Sydney Bryn
United States, Boston
Harvard T.h. Chan School of Public Health
United States, Boston
Boston Children's Hospital
United States, Boston
Channing Division of Network Medicine
United States, Boston
Harvard Medical School
Avdibegović, Esmina
Bosnia and Herzegovina, Tuzla
University Clinical Center Tuzla
BØRglum, Anders Dupont
Denmark, Aarhus
Aarhus Universitet
Babić, Dragan
Bosnia and Herzegovina, Mostar
University Clinical Hospital Mostar
Baekvad-Hansen, Marie
Denmark, Copenhagen
Statens Serum Institut
Baker, Dewleen G.
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Beckham, Jean C.
United States, Durham
Duke University School of Medicine
United States, Durham
Durham va Medical Center
Bierut, Laura Jean
United States, St. Louis
Washington University in St. Louis
Bisson, Jonathan I.
United Kingdom, London
Medical Research Council
Boks, Marco P.M.
Netherlands, Utrecht
University Medical Center Utrecht
Bolger, Elizabeth A.
United States, Boston
Harvard Medical School
United States, Belmont
Mclean Hospital
Bradley-Davino, Bekh B.
United States, Atlanta
Emory University School of Medicine
Brashear, Meghan M.
United States, New Orleans
Lsu Health Sciences Center - new Orleans
Breen, Gerome
United Kingdom, London
King's College London
Bryant, Richard A.
Australia, Sydney
Unsw Sydney
Bustamante, Angela C.
United States, Ann Arbor
University of Michigan Medical School
Bybjerg-Grauholm, Jonas
Denmark, Copenhagen
Statens Serum Institut
Calabrese, Joseph R.
United States, Cleveland
University Hospitals Case Medical Center
Caldas-de-Almeida, José M.
Portugal, Lisbon
Universidade Nova de Lisboa
Chen, Chia Yen
United States, Cambridge
Biogen Inc.
Dale, Anders M.
United States, La Jolla
University of California, San Diego
Dalvie, Shareefa
South Africa, Tygerberg
South African Medical Research Council
Deckert, Jürgen
Germany, Wurzburg
Universitätsklinikum Würzburg
Delahanty, Douglas L.
United States, Kent
Kent State University
Dennis, Michelle F.
United States, Durham
Duke University School of Medicine
United States, Durham
Durham va Medical Center
Disner, Seth G.
Unknown Affiliation
Domschke, Katharina
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Germany, Freiburg Im Breisgau
Universität Freiburg
Duncan, Laramie E.
United States, Palo Alto
Stanford University
Džubur Kulenović, Alma
Bosnia and Herzegovina, Sarajevo
Klinicki Centar Univerziteta u Sarajevu
Erbes, Christopher R.
United States, Minneapolis
University of Minnesota Twin Cities
Evans, Alexandra
United Kingdom, London
Medical Research Council
Farrer, Lindsay A.
United States, Boston
Boston University Chobanian & Avedisian School of Medicine
United States, Boston
School of Public Health
Feeny, Norah C.
United States, Cleveland
Case Western Reserve University
Flory, Janine Dyck
United States, New York
Icahn School of Medicine at Mount Sinai
Forbes, David
Australia, Melbourne
University of Melbourne
Franz, Carol E.
United States, La Jolla
University of California, San Diego
Galea, Sandro
United States, Boston
Boston University
Garrett, Melanie E.
United States, Durham
Duke University
Gautam, Aarti
Unknown Affiliation
Gelaye, Bizu S.
United States, Boston
Harvard T.h. Chan School of Public Health
Gelernter, Joel E.
United States, West Haven
Va Connecticut Healthcare System
United States, New Haven
Yale School of Medicine
Geuze, Elbert
Netherlands, Utrecht
University Medical Center Utrecht
Netherlands, The Hague
Ministerie Van Defensie
Gillespie, Charles F.
United States, Atlanta
Emory University School of Medicine
Goçi, Afërdita
Serbia, Pristina
University Clinical Center of Kosovo
Gordon, Scott D.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Guffanti, Guia
United States, Boston
Harvard Medical School
United States, Belmont
Mclean Hospital
Hammamieh, Rasha
Unknown Affiliation
Hauser, Michael A.
United States, Durham
Duke University School of Medicine
Heath, Andrew Christopher
United States, St. Louis
Washington University in St. Louis
Hemmings, Sian Megan Joanna
South Africa, Stellenbosch
Stellenbosch University
Hougaard, David Michael
Denmark, Copenhagen
Statens Serum Institut
Jakovljević, Miro
Croatia, Zagreb
Kbc Zagreb
Jett, Marti
United States, Silver Spring
Walter Reed Army Institute of Research
Johnson, Eric Otto
United States, Research Triangle Park
Rti International
Jones, Ian Richard G.
United Kingdom, London
Medical Research Council
Jovanović, Tanja
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Qin, Xuejun
United States, Durham
Duke University
Karstoft, Karen Inge
Denmark, Copenhagen
Københavns Universitet
Kaufman, Milissa L.
United States, Boston
Harvard Medical School
United States, Belmont
Mclean Hospital
Kessler, Ronald C.
United States, Boston
Harvard Medical School
Khan, Alaptagin
United States, Boston
Harvard Medical School
United States, Belmont
Mclean Hospital
Kimbrel, Nathan A.
United States, Durham
Duke University School of Medicine
United States, Durham
Durham va Medical Center
King, Anthony P.J.
United States, Ann Arbor
Michigan Medicine
Koen, Nastassja
South Africa, Tygerberg
South African Medical Research Council
Kranzler, Henry R.
United States
Va Medical Center
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
Kremen, William S.
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Lawford, Bruce Robert
Australia, Brisbane
Queensland University of Technology
Lebois, Lauren A.M.
United States, Boston
Harvard Medical School
United States, Belmont
Mclean Hospital
Lewis, Catrin E.
United Kingdom, London
Medical Research Council
Liberzon, Israel
United States, Bryan
Texas A&m University College of Medicine
Linnstaedt, Sarah D.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Logue, Mark W.
United States, Boston
Boston University Chobanian & Avedisian School of Medicine
United States, Boston
School of Public Health
United States
Va Medical Center
Lori, Adriana
United States, Atlanta
Emory University School of Medicine
Lugonja, Božo
United Kingdom, London
Medical Research Council
Luykx, Jurjen Justin
Netherlands, Utrecht
University Medical Center Utrecht
Lyons, Michael J.
United States, Boston
Boston University
Maples-Keller, Jessica L.
United States, Atlanta
Emory University School of Medicine
Marmar, Charles Raymond
United States, New York
Nyu Grossman School of Medicine
Martin, Nicholas G.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Maurer, Douglas M.
United States, Arlington
Association of the United States Army
Mavissakalian, Matig R.
United States, Cleveland
University Hospitals Case Medical Center
McFarlane, Alexander Cowell
Australia, Adelaide
The University of Adelaide
McGlinchey, Regina E.
United States
Va Medical Center
United States, Gainesville
Geriatric Research Education and Clinical Center
McLaughlin, Katie A.
United States, Cambridge
Harvard University
McLean, Samuel A.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Mellor, Rebecca
Australia, Greenslopes
Greenslopes Private Hospital
Michopoulos, V. J.
United States, Atlanta
Emory University School of Medicine
Milberg, William P.
United States
Va Medical Center
United States, Gainesville
Geriatric Research Education and Clinical Center
Miller, Mark W.
United States, Boston
Boston University Chobanian & Avedisian School of Medicine
United States
Va Medical Center
Morris, Charles Phillip
Australia, Brisbane
Queensland University of Technology
Australia, Brisbane
Metro North Hospital and Health Service
Mors, Ole N.
Denmark, Aarhus
Aarhus Universitetshospital
Mortensen, Preben Bo
Denmark, Aarhus
Aarhus Universitet
Nordentoft, Merete
Denmark, Copenhagen
Københavns Universitet
O'Donnell, Meaghan L.
Australia, Melbourne
University of Melbourne
Panizzon, Matthew S.
United States, La Jolla
University of California, San Diego
Peverill, Matthew
United States, Seattle
University of Washington
Pietrzak, Robert H.
United States, West Haven
Va Connecticut Healthcare System
United States, New Haven
Yale School of Medicine
Rice, John P.
United States, St. Louis
Washington University in St. Louis
Risbrough, Victoria B.
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Roberts, Andrea L.
United States, Boston
Harvard T.h. Chan School of Public Health
Rothbaum, Alex O.
United States, Cleveland
Case Western Reserve University
Rothbaum, Barbara Olasov
United States, Atlanta
Emory University School of Medicine
Roy-Byrne, Peter P.
United States, Seattle
University of Washington
Ruggiero, Kenneth J.
United States, Charleston
Medical University of South Carolina
Rutten, Bart PF F.
Netherlands, Maastricht
Maastricht Universitair Medisch Centrum+
Saccone, Nancy L.
United States, St. Louis
Washington University in St. Louis
Sánchez, Sixto E.
Peru, Lima
Universidad Peruana de Ciencias Aplicadas
Schijven, Dick
Netherlands, Utrecht
University Medical Center Utrecht
Seedat, Soraya
South Africa, Stellenbosch
Stellenbosch University
Seligowski, Antonia V.
United States, Boston
Harvard Medical School
United States, Belmont
Mclean Hospital
Sheerin, Christina M.
United States, Richmond
Virginia Institute for Psychiatric and Behavioral Genetics
Silove, Derrick M.
Australia, Sydney
Unsw Sydney
Smith, Alicia K.
United States, Atlanta
Emory University School of Medicine
Smoller, Jordan Wassertheil
United States, Boston
Massachusetts General Hospital
United States, Cambridge
Massachusetts Institute of Technology
Sponheim, Scott R.
United States, Minneapolis
University of Minnesota Twin Cities
Stein, Dan J.
South Africa, Tygerberg
South African Medical Research Council
Teicher, Martin Hersch
United States, Boston
Harvard Medical School
Thompson, Wesley Kurt
United States, San Diego
Human Longevity, Inc.
Denmark, Roskilde
Mental Health Centre Sct. Hans
Uddin, Monica
United States, Tampa
University of South Florida Health
Ursano, Robert J.
United States, Bethesda
Uniformed Services University of the Health Sciences
van den Heuvel, Leigh Luella
South Africa, Stellenbosch
Stellenbosch University
Van Hooff, Miranda L.
Australia, Adelaide
The University of Adelaide
Vermetten, E. H.G.J.M.
United States, New York
Nyu Grossman School of Medicine
Netherlands, The Hague
Ministerie Van Defensie
Netherlands, Diemen
Arq Psychotrauma Expert Group
Netherlands, Leiden
Leids Universitair Medisch Centrum
Vinkers, Christiaan H.
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Voisey, J.
Australia, Brisbane
Queensland University of Technology
Werge, Thomas M.
Denmark, Copenhagen
Københavns Universitet
Denmark, Copenhagen
Copenhagen University Hospital
Williams, Michelle A.
United States, Boston
Harvard T.h. Chan School of Public Health
Winternitz, Sherry R.
United States, Boston
Harvard Medical School
United States, Belmont
Mclean Hospital
Wolf, Christiane
Germany, Wurzburg
Universitätsklinikum Würzburg
Wolf, Erika J.
United States, Boston
Boston University Chobanian & Avedisian School of Medicine
United States
Va Medical Center
Yehuda, Rachel
United States, New York
Icahn School of Medicine at Mount Sinai
United States
Va Medical Center
Young, Ross Mc Donald
Australia, Brisbane
Queensland University of Technology
Australia, Brisbane
Metro North Hospital and Health Service
Zhao, Hongyu
United States, New Haven
Yale University
Zoellner, Lori A.
United States, Seattle
University of Washington
Haas, Magali
Unknown Affiliation
Provost, Allison C.
Unknown Affiliation
Salem, Rany M.
United States, La Jolla
University of California, San Diego
Shaffer, Richard A.
United States, San Diego
Naval Medical Center San Diego
Ripke, Stephan
United States, Boston
Massachusetts General Hospital
United States, Cambridge
Massachusetts Institute of Technology
Germany, Berlin
Charité – Universitätsmedizin Berlin
Daly, Mark J.
United States, Boston
Massachusetts General Hospital
Ressler, Kerry James
United States, Boston
Harvard Medical School
United States, Belmont
Mclean Hospital
United States, Atlanta
Emory University School of Medicine
Koenen, Karestan Chase
United States, Boston
Harvard T.h. Chan School of Public Health
United States, Boston
Massachusetts General Hospital
United States, Cambridge
Massachusetts Institute of Technology
Stein, Murray B.
United States, La Jolla
University of California, San Diego
United States, San Diego
Human Longevity, Inc.
United States, San Diego
Va San Diego Healthcare System
Nievergelt, Caroline M.
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Statistics
Citations: 13
Authors: 163
Affiliations: 96
Identifiers
Doi:
10.1016/j.biopsych.2021.09.020
ISSN:
00063223
Research Areas
Genetics And Genomics
Mental Health
Study Design
Cohort Study
Case-Control Study
Study Approach
Quantitative
Systematic review