Enhancing discovery of genetic variants for PTSD through integration of quantitative phenotypes and trauma exposure information

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Adam X. Maihofer
  • Karmel W. Choi
  • Jonathan R.I. Coleman
  • Nikolaos P. Daskalakis
  • Christy A. Denckla
  • Elizabeth Ketema
  • Rajendra A. Morey
  • Renato Polimanti
  • Andrew Ratanatharathorn
  • Katy Torres
  • Aliza P. Wingo
  • Clement C. Zai
  • Allison E. Aiello
  • Lynn M. Almli
  • Ananda B. Amstadter
  • Soren B. Andersen
  • Ole A. Andreassen
  • Paul A. Arbisi
  • Allison E. Ashley-Koch
  • S. Bryn Austin
  • Esmina Avdibegovic
  • Anders D. Borglum
  • Dragan Babic
  • Marie Bμkvad-Hansen
  • Dewleen G. Baker
  • Jean C. Beckham
  • Laura J. Bierut
  • Jonathan I. Bisson
  • Marco P. Boks
  • Elizabeth A. Bolger
  • Bekh Bradley
  • Meghan Brashear
  • Gerome Breen
  • Richard A. Bryant
  • Angela C. Bustamante
  • Jonas Bybjerg-Grauholm
  • Joseph R. Calabrese
  • J.M. Caldas-de-Almeida
  • Chia-Yen Chen
  • Anders M. Dale
  • Shareefa Dalvie
  • Jürgen Deckert
  • Douglas L. Delahanty
  • Michelle F. Dennis
  • Seth G. Disner
  • Katharina Domschke
  • Laramie E. Duncan
  • Alma Dzubur Kulenovic
  • Christopher R. Erbes
  • Alexandra Evans
  • Lindsay A. Farrer
  • Norah C. Feeny
  • Janine D. Flory
  • David Forbes
  • Carol E. Franz
  • Sandro Galea
  • Melanie E. Garrett
  • Aarti Gautam
  • Bizu Gelaye
  • Joel Gelernter
  • Elbert Geuze
  • Charles F. Gillespie
  • Aferdita Goci
  • Scott D. Gordon
  • Guia Guffanti
  • Rasha Hammamieh
  • Michael A. Hauser
  • Andrew C. Heath
  • Sian M.J. Hemmings
  • David Michael Hougaard
  • Miro Jakovljevic
  • Marti Jett
  • Eric Otto Johnson
  • Ian Jones
  • Tanja Jovanovic
  • Xue-Jun Qin
  • Milissa L. Kaufman
  • Ronald C. Kessler
  • Alaptagin Khan
  • Nathan A. Kimbrel
  • Anthony P. King
  • Nastassja Koen
  • Henry R. Kranzler
  • William S. Kremen
  • Bruce R. Lawford
  • Lauren A.M. Lebois
  • Catrin Lewis
  • Israel Liberzon
  • Sarah D. Linnstaedt
  • Mark W. Logue
  • Adriana Lori
  • Bozo Lugonja
  • Jurjen J. Luykx
  • Michael J. Lyons
  • Jessica L. Maples-Keller
  • Charles Marmar
  • Nicholas G. Martin
  • D. Maurer
  • Matig R. Mavissakalian
  • Alexander McFarlane
  • Regina E. McGlinchey
  • Katie A. McLaughlin
  • Samuel A. McLean
  • Divya Mehta
  • Rebecca Mellor
  • Vasiliki Michopoulos
  • William Milberg
  • Mark W. Miller
  • Charles Phillip Morris
  • Ole Mors
  • P.B. Mortensen
  • Elliot C. Nelson
  • Sonya B. Norman
  • Meaghan O'Donnell
  • Holly K. Orcutt
  • Matthew S. Panizzon
  • Edward S. Peters
  • Alan L. Peterson
  • Matthew Peverill
  • Robert H. Pietrzak
  • Melissa A. Polusny
  • John P. Rice
  • Victoria B. Risbrough
  • Andrea L. Roberts
  • Alex O. Rothbaum
  • Barbara O. Rothbaum
  • P. Roy-Byrne
  • Kenneth J. Ruggiero
  • Ariane Rung
  • Bart P.F. Rutten
  • Nancy L. Saccone
  • Sixto E. Sanchez
  • Dick Schijven
  • S. Seedat
  • Antonia V. Seligowski
  • Julia S. Seng
  • Christina M. Sheerin
  • Derrick Silove
  • Alicia K. Smith
  • Jordan W. Smoller
  • Scott R. Sponheim
  • Dan J. Stein
  • Jennifer S. Stevens
  • Martin H. Teicher
  • Wesley K. Thompson
  • Edward Trapido
  • Monica Uddin
  • Robert J. Ursano
  • Leigh Luella van den Heuvel
  • Miranda Van Hooff
  • Eric Vermetten
  • Christiaan Vinkers
  • Joanne Voisey
  • Yunpeng Wang
  • Zhewu Wang
  • Michelle A. Williams
  • Douglas E. Williamson
  • Sherry Winternitz
  • Christiane Wolf
  • Erika J. Wolf
  • Rachel Yehuda
  • Keith A. Young
  • Ross McD. Young
  • Hongyu Zhao
  • Lori A. Zoellner
  • Magali Haas
  • Heather Lasseter
  • Allison C. Provost
  • Rany M. Salem
  • Jonathan Sebat
  • Richard A. Shaffer
  • Tianying Wu
  • Stephan Ripke
  • Mark J. Daly
  • Kerry J. Ressler
  • Karestan C. Koenen
  • Murray B. Stein
  • Caroline M. Nievergelt
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 (GWAS). Methods 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 LD-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 (MVP) GWAS of PTSD total symptoms. Results GWAS 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 out of these 9 PTSD loci were independently replicated in MVP. Conclusion Through using a quantitative trait measure of PTSD, we identify 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.
OriginalsprogDansk
TidsskriftBiological Psychiatry
ISSN0006-3223
DOI
StatusUdgivet - 2021

    Forskningsområder

  • PTSD, GWAS, trauma, genetics, PheWAS, heritability

ID: 285378522