1. Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder
- Author
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Nievergelt, Caroline M., Maihofer, Adam X., Atkinson, Elizabeth G., Chen, Chia-Yen, Choi, Karmel W., Coleman, Jonathan R. I., 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, Babić, 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., Desarnaud, Frank, DiPietro, Christopher P., Disner, Seth G., Docherty, Anna R., Domschke, Katharina, Dyb, Grete, Kulenović, Alma Džubur, 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., Goleva, Slavina B., Gordon, Scott D., Goçi, Aferdita, Grasser, Lana Ruvolo, Guindalini, Camila, Haas, Magali, Hagenaars, Saskia, Hauser, Michael A., Heath, Andrew C., Hemmings, Sian M. J., Hesselbrock, Victor, Hickie, Ian B., Hogan, Kelleigh, Hougaard, David Michael, Huang, Hailiang, Huckins, Laura M., Hveem, Kristian, Jakovljević, 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, Alex O., Rothbaum, Barbara 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 Hooff, Miranda, Vermetten, Eric, Vinkers, Christiaan H., Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Waszczuk, Monika, Weber, Heike, Wendt, Frank R., Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winsvold, Bendik S., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Xia, Yan, Xiong, Ying, Yehuda, Rachel, Young, Keith A., Young, Ross McD, Zai, Clement C., Zai, Gwyneth C., Zervas, Mark, Zhao, Hongyu, Zoellner, Lori A., Zwart, John-Anker, deRoon-Cassini, Terri, van Rooij, Sanne J. H., van den Heuvel, Leigh L., Stein, Murray B., Ressler, Kerry J., and Koenen, Karestan C.
- 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, GRM8and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5and DCC), synaptic structure and function genes (for example, PCLO, NCAM1and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3and 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.
- Published
- 2024
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