Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders.

Authors

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

Year

2023

Journal

medRxiv : the preprint server for health sciences

PMID

37693460

DOI

10.1101/2023.08.31.23294915

PMCID

PMC10491375

Posttraumatic 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 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., ), developmental, axon guidance, and transcription factors (e.g., ), synaptic structure and function genes (e.g., ), and endocrine or immune regulators (e.g., ). 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.

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