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

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; Daniel F Levey; Mark W Logue; Renato Polimanti; Allison C Provost; Andrew Ratanatharathorn; Murray B Stein; Katy Torres; 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; Dragan Babic; Marie Bækvad-Hansen; Dewleen G Baker; Jean C Beckham; Laura J Bierut; Jonathan I Bisson; Marco P Boks; Elizabeth A Bolger; Anders D Børglum; Bekh Bradley; Megan Brashear; Gerome Breen; Richard A Bryant; Angela C Bustamante; Jonas Bybjerg-Grauholm; Joseph R Calabrese; Jose M Caldas-de-Almeida; Anders M Dale; Mark J Daly; Nikolaos P Daskalakis; Jürgen Deckert; Douglas L Delahanty; Michelle F Dennis; Seth G Disner; Katharina Domschke; Alma Dzubur-Kulenovic; Christopher R Erbes; Alexandra Evans; Lindsay A Farrer; Norah C Feeny; Janine D Flory; David Forbes; Carol Franz; Sandro Galea; Melanie E Garrett; Bizu Gelaye; Elbert Geuze; Charles Gillespie; Agerdita Goci Uka; Scott D Gordon; Guia Guffanti; Rasha Hammamieh; Supriya Harnal; 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; Angela G Junglen; Karen-Inge Karstoft; Milissa L Kaufman; Ronald C Kessler; Alaptagin Khan; Nathan A Kimbrel; Anthony King; Nastassja Koen; Henry R Kranzler; William S Kremen; Bruce R Lawford; Lauren A M Lebois; Catrin E Lewis; Sarah D Linnstaedt; Adriana Lori; Bozo Lugonja; Jurjen J Luykx; Michael J Lyons; Jessica Maples-Keller; Charles Marmar; Alicia R Martin; Nicholas G Martin; Douglas Maurer; Matig R Mavissakalian; Alexander C McFarlane; Regina E McGlinchey; Katie McLaughlin; Samuel A McLean; Sarah McLeay; Divya Mehta; William P Milberg; Mark W Miller; Rajendra Morey; Charles Phillip Morris; Ole Mors; Preben B Mortensen; Benjamin M Neale; Elliot C Nelson; Merete Nordentoft; Sonya B Norman; Meaghan L O'Donnell; Holly K Orcutt; Matthew S Panizzon; Edward S Peters; Alan L Peterson; Matthew Peverill; Robert H Pietrzak; Melissa A Polusny; John Rice; S Ripke; Victoria B Risbrough; Andrea L Roberts; Alex O Rothbaum; Barbara O Rothbaum; Peter Roy-Byrne; Ken Ruggiero; Ariane Rung; Bart P F Rutten; Nancy L Saccone; Sixto E Sanchez; Dick Schijven; Soraya 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 Stevens; Jennifer A Sumner; Martin J Teicher; Wesley K Thompson; Edward Trapido; Monica Uddin; Robert J Ursano; Leigh van den Heuvel; Miranda Van Hooff; Eric Vermetten; Christiaan H Vinkers; Joanne Voisey; Yunpeng Wang; Zhewu Wang; Thomas Werge; Michelle A Williams; Douglas E Williamson; Sherry R Winternitz; Christiane Wolf; Erika J Wolf; Jonathan D Wolff; Rachel Yehuda; Ross Young; See article text for complete list of authors.

doi:10.1038/s41467-019-12576-w

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

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

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, …

Nature Communications, Vol.10, pp.1-16

2019

DOI: https://doi.org/10.1038/s41467-019-12576-w

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Abstract

Behavioural genetics

genetics of the nervous system

genome-wide association studies

post-traumatic stress disorder

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.

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Title: International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci
Authors: Caroline M Nievergelt (Corresponding Author) - University of California, San Diego
Adam X Maihofer (Author) - University of California, San Diego
Torsten Klengel (Author) - Harvard Medical School
Elizabeth G Atkinson (Author) - Harvard University
Chia-Yen Chen (Author) - Harvard University
Karmel W Choi (Author) - Harvard University
Jonathan R I Coleman (Author) - King's College London
Shareefa Dalvie (Author) - University of Cape Town
Laramie E Duncan (Author) - Stanford University
Joel Gelernter (Author) - Yale University
Daniel F Levey (Author) - Yale University
Mark W Logue (Author) - VA Boston Healthcare System
Renato Polimanti (Author) - Yale University
Allison C Provost (Author) - Cohen Veterans Bioscience
Andrew Ratanatharathorn (Author) - Harvard University
Murray B Stein (Author) - University of California, San Diego
Katy Torres (Author)
Allison E Aiello (Author) - Gillings School of Global Public Health
Lynn M Almli (Author)
Ananda B Amstadter (Author) - Virginia Institute for Psychiatric and Behavioral Genetics
Soren B Andersen (Author) - Danish Veteran Centre
Ole A Andreassen (Author) - University of Oslo
Paul A Arbisi (Author) - Minneapolis VA Health Care System
Allison E Ashley-Koch (Author) - Duke University
S Bryn Austin (Author) - Harvard Medical School
Esmina Avdibegovic (Author) - University Clinical Center Tuzla
Dragan Babic (Author) - University Clinical Hospital Mostar
Marie Bækvad-Hansen (Author) - Lundbeck Foundation
Dewleen G Baker (Author) - University of California, San Diego
Jean C Beckham (Author) - Duke University
Laura J Bierut (Author) - Washington University in St. Louis School of Medicine
Jonathan I Bisson (Author) - Cardiff University
Marco P Boks (Author) - UMC Utrecht Brain Center Rudolf Magnus
Elizabeth A Bolger (Author) - Harvard Medical School
Anders D Børglum (Author) - Aarhus University
Bekh Bradley (Author) - Emory University
Megan Brashear (Author) - Louisiana State University Health Sciences Center New Orleans
Gerome Breen (Author) - King's College London
Richard A Bryant (Author) - UNSW Australia
Angela C Bustamante (Author) - University of Michigan Medical School
Jonas Bybjerg-Grauholm (Author)
Joseph R Calabrese (Author) - Cleveland University
Jose M Caldas-de-Almeida (Author)
Anders M Dale (Author) - University of California, San Diego
Mark J Daly (Author)
Nikolaos P Daskalakis (Author) - Harvard Medical School
Jürgen Deckert (Author) - University Hospital of Würzburg
Douglas L Delahanty (Author)
Michelle F Dennis (Author) - Duke University
Seth G Disner (Author) - Minneapolis VA Health Care System
Katharina Domschke (Author) - University of Freiburg
Alma Dzubur-Kulenovic (Author)
Christopher R Erbes (Author) - University of Minnesota
Alexandra Evans (Author) - Cardiff University
Lindsay A Farrer (Author) - Boston University School of Medicine
Norah C Feeny (Author) - Case Western Reserve University
Janine D Flory (Author) - Icahn School of Medicine at Mount Sinai
David Forbes (Author) - The University of Melbourne
Carol Franz (Author) - University of California, San Diego
Sandro Galea (Author) - Boston University
Melanie E Garrett (Author) - Duke University
Bizu Gelaye (Author)
Elbert Geuze (Author) - UMC Utrecht Brain Center Rudolf Magnus
Charles Gillespie (Author) - Emory University
Agerdita Goci Uka (Author) - University Clinical Center of Kosovo
Scott D Gordon (Author) - QIMR Berghofer Medical Research Institute
Guia Guffanti (Author) - Harvard Medical School
Rasha Hammamieh (Author) - United States Army Medical Research and Development Command
Supriya Harnal (Author) - Broad Institute
Michael A Hauser (Author) - Duke University
Andrew C Heath (Author) - Washington University in St. Louis
Sian M J Hemmings (Author) - Stellenbosch University
David Michael Hougaard (Author) - Statens Serum Institut
Miro Jakovljevic (Author) - University of Zagreb
Marti Jett (Author) - 61USC_INST___USACEHR
Eric Otto Johnson (Author) - RTI International
Ian Jones (Author)
Tanja Jovanovic (Author) - Emory University
Xue-Jun Qin (Author)
Angela G Junglen (Author) - Kent State University
Karen-Inge Karstoft (Author) - Danish Veteran Centre
Milissa L Kaufman (Author) - Harvard Medical School
Ronald C Kessler (Author) - Harvard Medical School
Alaptagin Khan (Author) - Harvard Medical School
Nathan A Kimbrel (Author) - Duke University
Anthony King (Author) - University of Michigan Medical School
Nastassja Koen (Author) - University of Cape Town
Henry R Kranzler (Author) - University of Pennsylvania
William S Kremen (Author) - University of California, San Diego
Bruce R Lawford (Author) - Queensland University of Technology
Lauren A M Lebois (Author) - Harvard Medical School
Catrin E Lewis (Author) - Cardiff University
Sarah D Linnstaedt (Author) - UNC Institute for Trauma Recovery
Adriana Lori (Author) - Emory University
Bozo Lugonja (Author) - Cardiff University
Jurjen J Luykx (Author) - UMC Utrecht Brain Center Rudolf Magnus
Michael J Lyons (Author) - Boston University
Jessica Maples-Keller (Author) - Emory University
Charles Marmar (Author) - New York University School of Medicine
Alicia R Martin (Author) - Massachusetts General Hospital
Nicholas G Martin (Author) - QIMR Berghofer Medical Research Institute
Douglas Maurer (Author) - United States Army
Matig R Mavissakalian (Author) - Cleveland University
Alexander C McFarlane (Author) - The University of Adelaide
Regina E McGlinchey (Author) - VA Boston Healthcare System
Katie McLaughlin (Author) - Harvard University
Samuel A McLean (Author) - UNC Institute for Trauma Recovery
Sarah McLeay (Author) - Greenslopes Private Hospital
Divya Mehta (Author) - Queensland University of Technology
William P Milberg (Author) - VA Boston Healthcare System
Mark W Miller (Author) - National Center for Post Traumatic Stress Disorder
Rajendra Morey (Author) - Duke University
Charles Phillip Morris (Author) - Queensland University of Technology
Ole Mors (Author) - Aarhus University Hospital
Preben B Mortensen (Author) - Aarhus University
Benjamin M Neale (Author) - Massachusetts General Hospital
Elliot C Nelson (Author) - Washington University in St. Louis
Merete Nordentoft (Author) - University of Copenhagen
Sonya B Norman (Author) - University of California, San Diego
Meaghan L O'Donnell (Author) - The University of Melbourne
Holly K Orcutt (Author) - Northern Illinois University
Matthew S Panizzon (Author) - University of California, San Diego
Edward S Peters (Author) - Louisiana State University Health Sciences Center New Orleans
Alan L Peterson (Author) - The University of Texas Health Science Center at San Antonio
Matthew Peverill (Author) - University of Washington
Robert H Pietrzak (Author) - Yale University
Melissa A Polusny (Author) - Minneapolis VA Health Care System
John Rice (Author) - Washington University in St. Louis
S Ripke (Author) - Broad Institute
Victoria B Risbrough (Author)
Andrea L Roberts (Author)
Alex O Rothbaum (Author) - Case Western Reserve University
Barbara O Rothbaum (Author) - Emory University
Peter Roy-Byrne (Author) - University of Washington
Ken Ruggiero (Author) - Medical University of South Carolina
Ariane Rung (Author) - Louisiana State University Health Sciences Center New Orleans
Bart P F Rutten (Author) - Maastricht University
Nancy L Saccone (Author) - Washington University in St. Louis School of Medicine
Sixto E Sanchez (Author) - Universidad Peruana de Ciencias Aplicadas
Dick Schijven (Author) - UMC Utrecht Brain Center Rudolf Magnus
Soraya Seedat (Author) - Stellenbosch University
Antonia V Seligowski (Author) - Harvard Medical School
Julia S Seng (Author) - University of Michigan Medical School
Christina M Sheerin (Author) - Virginia Institute for Psychiatric and Behavioral Genetics
Derrick Silove (Author) - UNSW Australia
Alicia K Smith (Author) - Emory University
Jordan W Smoller (Author) - Massachusetts General Hospital
Scott R Sponheim (Author) - University of Minnesota
Dan J Stein (Author) - University of Cape Town
Jennifer Stevens (Author) - Emory University
Jennifer A Sumner (Author) - Columbia University Irving Medical Center
Martin J Teicher (Author) - Harvard Medical School
Wesley K Thompson (Author) - University of California, San Diego
Edward Trapido (Author) - Louisiana State University
Monica Uddin (Author) - University of Florida
Robert J Ursano (Author) - Uniformed Services University of the Health Sciences
Leigh van den Heuvel (Author) - Stellenbosch University
Miranda Van Hooff (Author) - The University of Adelaide
Eric Vermetten (Author) - Leiden University
Christiaan H Vinkers (Author) - Amsterdam UMC - Vrije Universiteit Amsterdam
Joanne Voisey (Author) - Queensland University of Technology
Yunpeng Wang (Author) - Oslo University Hospital
Zhewu Wang (Author) - Ralph H. Johnson VA Medical Center
Thomas Werge (Author) - Lundbeck Foundation
Michelle A Williams (Author) - Harvard T.H. Chan School of Public Health
Douglas E Williamson (Author) - Duke University
Sherry R Winternitz (Author) - Harvard Medical School
Christiane Wolf (Author) - University Hospital of Würzburg
Erika J Wolf (Author) - VA Boston Healthcare System
Jonathan D Wolff (Author) - McLean Hospital
Rachel Yehuda (Author) - Icahn School of Medicine at Mount Sinai
Ross Young (Author) - University of the Sunshine Coast, Queensland, Office of the Deputy Vice-Chancellor (Research and Innovation)
See article text for complete list of authors. (Author)
Publication details: Nature Communications, Vol.10, pp.1-16
Publisher: Nature Publishing Group
Date published: 2019
DOI: 10.1038/s41467-019-12576-w
ISSN: 2041-1723
Copyright note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Organisation Unit: University of the Sunshine Coast, Queensland; Office of the Deputy Vice-Chancellor (Research and Innovation)
Language: English
Record Identifier: 99622041002621
Output Type: Journal article

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