Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder

Caroline M. Nievergelt, Adam X. Maihofer, Elizabeth G. Atkinson, Chia Yen Chen, Karmel W. Choi, Jonathan R.I. Coleman, Nikolaos P. Daskalakis, Laramie E. Duncan, Renato Polimanti, Cindy Aaronson, Ananda B. Amstadter, Soren B. Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley-Koch, S. Bryn Austin, Esmina Avdibegoviç, Dragan Babić, Silviu Alin Bacanu, Dewleen G. BakerAnthony Batzler, Jean C. Beckham, Sintia Belangero, Corina Benjet, Carisa Bergner, Linda M. Bierer, Joanna M. Biernacka, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth A. Bolger, Amber Brandolino, Gerome Breen, Rodrigo Affonseca Bressan, Richard A. Bryant, Angela C. Bustamante, Jonas Bybjerg-Grauholm, Marie Bækvad-Hansen, Anders D. Børglum, Sigrid Børte, Leah Cahn, Joseph R. Calabrese, Jose Miguel Caldas-de-Almeida, Chris Chatzinakos, Sheraz Cheema, Sean A.P. Clouston, Lucía Colodro-Conde, Brandon J. Coombes, Carlos S. Cruz-Fuentes, Anders M. Dale, Shareefa Dalvie, Lea K. Davis, Jürgen Deckert, Douglas L. Delahanty, Michelle F. Dennis, Frank Desarnaud, Christopher P. DiPietro, Seth G. Disner, Anna R. Docherty, Katharina Domschke, Grete Dyb, Alma Džubur Kulenović, Howard J. Edenberg, Alexandra Evans, Chiara Fabbri, Negar Fani, Lindsay A. Farrer, Adriana Feder, Norah C. Feeny, Janine D. Flory, David Forbes, Carol E. Franz, Sandro Galea, Melanie E. Garrett, Bizu Gelaye, Joel Gelernter, Elbert Geuze, Charles F. Gillespie, Slavina B. Goleva, Scott D. Gordon, Aferdita Goçi, Lana Ruvolo Grasser, Camila Guindalini, Magali Haas, Saskia Hagenaars, Michael A. Hauser, Andrew C. Heath, Sian M.J. Hemmings, Victor Hesselbrock, Ian B. Hickie, Kelleigh Hogan, David Michael Hougaard, Hailiang Huang, Laura M. Huckins, Kristian Hveem, Miro Jakovljević, Arash Javanbakht, Gregory D. Jenkins, Jessica Johnson, Ian Jones, Tanja Jovanovic, Karen Inge Karstoft, Milissa L. Kaufman, James L. Kennedy, Ronald C. Kessler, Alaptagin Khan, Nathan A. Kimbrel, Anthony P. King, Nastassja Koen, Roman Kotov, Henry R. Kranzler, Kristi Krebs, William S. Kremen, Pei Fen Kuan, Bruce R. Lawford, Lauren A.M. Lebois, Kelli Lehto, Daniel F. Levey, Catrin Lewis, Israel Liberzon, Sarah D. Linnstaedt, Mark W. Logue, Adriana Lori, Yi Lu, Benjamin J. Luft, Michelle K. Lupton, Jurjen J. Luykx, Iouri Makotkine, Jessica L. Maples-Keller, Shelby Marchese, Charles Marmar, Nicholas G. Martin, Gabriela A. Martínez-Levy, Kerrie McAloney, Alexander McFarlane, Katie A. McLaughlin, Samuel A. McLean, Sarah E. Medland, Divya Mehta, Jacquelyn Meyers, Vasiliki Michopoulos, Elizabeth A. Mikita, Lili Milani, William Milberg, Mark W. Miller, Rajendra A. Morey, Charles Phillip Morris, Ole Mors, Preben Bo Mortensen, Mary S. Mufford, Elliot C. Nelson, Merete Nordentoft, Sonya B. Norman, Nicole R. Nugent, Meaghan O’Donnell, Holly K. Orcutt, Pedro M. Pan, Matthew S. Panizzon, Gita A. Pathak, Edward S. Peters, Alan L. Peterson, Matthew Peverill, Robert H. Pietrzak, Melissa A. Polusny, Bernice Porjesz, Abigail Powers, Xue Jun Qin, Andrew Ratanatharathorn, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy-Byrne, Kenneth J. Ruggiero, Ariane Rung, Heiko Runz, Bart P.F. Rutten, Stacey Saenz de Viteri, Giovanni Abrahão Salum, Laura Sampson, Sixto E. Sanchez, Marcos Santoro, Carina Seah, Soraya Seedat, Julia S. Seng, Andrey Shabalin, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Scott R. Sponheim, Dan J. Stein, Synne Stensland, Jennifer S. Stevens, Jennifer A. Sumner, Martin H. Teicher, Wesley K. Thompson, Arun K. Tiwari, Edward Trapido, Monica Uddin, Robert J. Ursano, Unnur Valdimarsdóttir, Miranda Van Hooff, Eric Vermetten, Christiaan H. Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Monika Waszczuk, Heike Weber, Frank R. Wendt, Thomas Werge, Michelle A. Williams, Douglas E. Williamson, Bendik S. Winsvold, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Yan Xia, Ying Xiong, Rachel Yehuda, Keith A. Young, Ross Mc D. Young, Gwyneth C. Zai, Gwyneth C. Zai, Mark Zervas, Hongyu Zhao, Lori A. Zoellner, John Anker Zwart, Terri deRoon-Cassini, Sanne J.H. van Rooij, Leigh L. van den Heuvel, Murray B. Stein, Kerry J. Ressler, Karestan C. Koenen

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4 Citations (Scopus)

Abstract

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Original languageEnglish
JournalNature Genetics
DOIs
Publication statusE-pub ahead of print - 18 Apr 2024

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