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. Baker; Anthony 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; Clement 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

doi:10.1038/s41588-024-01707-9

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, Clement 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

Department of Psychiatry & Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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 language	English (US)
Pages (from-to)	792-808
Number of pages	17
Journal	Nature Genetics
Volume	56
Issue number	5
DOIs	https://doi.org/10.1038/s41588-024-01707-9
State	Published - May 2024

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/s41588-024-01707-9

Cite this

Nievergelt, C. M., Maihofer, A. X., Atkinson, E. G., Chen, C. Y., Choi, K. W., Coleman, J. R. I., Daskalakis, N. P., Duncan, L. E., Polimanti, R., Aaronson, C., Amstadter, A. B., Andersen, S. B., Andreassen, O. A., Arbisi, P. A., Ashley-Koch, A. E., Austin, S. B., Avdibegoviç, E., Babić, D., Bacanu, S. A., ... Koenen, K. C. (2024). Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. Nature Genetics, 56(5), 792-808. https://doi.org/10.1038/s41588-024-01707-9

Nievergelt, CM, Maihofer, AX, Atkinson, EG, Chen, CY, Choi, KW, Coleman, JRI, Daskalakis, NP, Duncan, LE, Polimanti, R, Aaronson, C, Amstadter, AB, Andersen, SB, Andreassen, OA, Arbisi, PA, Ashley-Koch, AE, Austin, SB, Avdibegoviç, E, Babić, D, Bacanu, SA, Baker, DG, Batzler, A, Beckham, JC, Belangero, S, Benjet, C, Bergner, C, Bierer, LM, Biernacka, JM, Bierut, LJ, Bisson, JI, Boks, MP, Bolger, EA, Brandolino, A, Breen, G, Bressan, RA, Bryant, RA, Bustamante, AC, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Børglum, AD, Børte, S, Cahn, L, Calabrese, JR, Caldas-de-Almeida, JM, Chatzinakos, C, Cheema, S, Clouston, SAP, Colodro-Conde, L, Coombes, BJ, Cruz-Fuentes, CS, Dale, AM, Dalvie, S, Davis, LK, Deckert, J, Delahanty, DL, Dennis, MF, Desarnaud, F, DiPietro, CP, Disner, SG, Docherty, AR, Domschke, K, Dyb, G, Kulenović, AD, Edenberg, HJ, Evans, A, Fabbri, C, Fani, N, Farrer, LA, Feder, A, Feeny, NC, Flory, JD, Forbes, D, Franz, CE, Galea, S, Garrett, ME, Gelaye, B, Gelernter, J, Geuze, E, Gillespie, CF, Goleva, SB, Gordon, SD, Goçi, A, Grasser, LR, Guindalini, C, Haas, M, Hagenaars, S, Hauser, MA, Heath, AC, Hemmings, SMJ, Hesselbrock, V, Hickie, IB, Hogan, K, Hougaard, DM, Huang, H, Huckins, LM, Hveem, K, Jakovljević, M, Javanbakht, A, Jenkins, GD, Johnson, J, Jones, I, Jovanovic, T, Karstoft, KI, Kaufman, ML, Kennedy, JL, Kessler, RC, Khan, A, Kimbrel, NA, King, AP, Koen, N, Kotov, R, Kranzler, HR, Krebs, K, Kremen, WS, Kuan, PF, Lawford, BR, Lebois, LAM, Lehto, K, Levey, DF, Lewis, C, Liberzon, I, Linnstaedt, SD, Logue, MW, Lori, A, Lu, Y, Luft, BJ, Lupton, MK, Luykx, JJ, Makotkine, I, Maples-Keller, JL, Marchese, S, Marmar, C, Martin, NG, Martínez-Levy, GA, McAloney, K, McFarlane, A, McLaughlin, KA, McLean, SA, Medland, SE, Mehta, D, Meyers, J, Michopoulos, V, Mikita, EA, Milani, L, Milberg, W, Miller, MW, Morey, RA, Morris, CP, Mors, O, Mortensen, PB, Mufford, MS, Nelson, EC, Nordentoft, M, Norman, SB, Nugent, NR, O’Donnell, M, Orcutt, HK, Pan, PM, Panizzon, MS, Pathak, GA, Peters, ES, Peterson, AL, Peverill, M, Pietrzak, RH, Polusny, MA, Porjesz, B, Powers, A, Qin, XJ, Ratanatharathorn, A, Risbrough, VB, Roberts, AL, Rothbaum, AO, Rothbaum, BO, Roy-Byrne, P, Ruggiero, KJ, Rung, A, Runz, H, Rutten, BPF, de Viteri, SS, Salum, GA, Sampson, L, Sanchez, SE, Santoro, M, Seah, C, Seedat, S, Seng, JS, Shabalin, A, Sheerin, CM, Silove, D, Smith, AK, Smoller, JW, Sponheim, SR, Stein, DJ, Stensland, S, Stevens, JS, Sumner, JA, Teicher, MH, Thompson, WK, Tiwari, AK, Trapido, E, Uddin, M, Ursano, RJ, Valdimarsdóttir, U, Van Hooff, M, Vermetten, E, Vinkers, CH, Voisey, J, Wang, Y, Wang, Z, Waszczuk, M, Weber, H, Wendt, FR, Werge, T, Williams, MA, Williamson, DE, Winsvold, BS, Winternitz, S, Wolf, C, Wolf, EJ, Xia, Y, Xiong, Y, Yehuda, R, Young, KA, Young, RMD, Zai, CC, Zai, GC, Zervas, M, Zhao, H, Zoellner, LA, Zwart, JA, deRoon-Cassini, T, van Rooij, SJH, van den Heuvel, LL, Stein, MB, Ressler, KJ & Koenen, KC 2024, 'Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder', Nature Genetics, vol. 56, no. 5, pp. 792-808. https://doi.org/10.1038/s41588-024-01707-9

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

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.",

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

note = "Publisher Copyright: {\textcopyright} This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.",

year = "2024",

month = may,

doi = "10.1038/s41588-024-01707-9",

language = "English (US)",

volume = "56",

pages = "792--808",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

}

TY - JOUR

T1 - Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder

AU - Nievergelt, Caroline M.

AU - Maihofer, Adam X.

AU - Atkinson, Elizabeth G.

AU - Chen, Chia Yen

AU - Choi, Karmel W.

AU - Coleman, Jonathan R.I.

AU - Daskalakis, Nikolaos P.

AU - Duncan, Laramie E.

AU - Polimanti, Renato

AU - Aaronson, Cindy

AU - Amstadter, Ananda B.

AU - Andersen, Soren B.

AU - Andreassen, Ole A.

AU - Arbisi, Paul A.

AU - Ashley-Koch, Allison E.

AU - Austin, S. Bryn

AU - Avdibegoviç, Esmina

AU - Babić, Dragan

AU - Bacanu, Silviu Alin

AU - Baker, Dewleen G.

AU - Batzler, Anthony

AU - Beckham, Jean C.

AU - Belangero, Sintia

AU - Benjet, Corina

AU - Bergner, Carisa

AU - Bierer, Linda M.

AU - Biernacka, Joanna M.

AU - Bierut, Laura J.

AU - Bisson, Jonathan I.

AU - Boks, Marco P.

AU - Bolger, Elizabeth A.

AU - Brandolino, Amber

AU - Breen, Gerome

AU - Bressan, Rodrigo Affonseca

AU - Bryant, Richard A.

AU - Bustamante, Angela C.

AU - Bybjerg-Grauholm, Jonas

AU - Bækvad-Hansen, Marie

AU - Børglum, Anders D.

AU - Børte, Sigrid

AU - Cahn, Leah

AU - Calabrese, Joseph R.

AU - Caldas-de-Almeida, Jose Miguel

AU - Chatzinakos, Chris

AU - Cheema, Sheraz

AU - Clouston, Sean A.P.

AU - Colodro-Conde, Lucía

AU - Coombes, Brandon J.

AU - Cruz-Fuentes, Carlos S.

AU - Dale, Anders M.

AU - Dalvie, Shareefa

AU - Davis, Lea K.

AU - Deckert, Jürgen

AU - Delahanty, Douglas L.

AU - Dennis, Michelle F.

AU - Desarnaud, Frank

AU - DiPietro, Christopher P.

AU - Disner, Seth G.

AU - Docherty, Anna R.

AU - Domschke, Katharina

AU - Dyb, Grete

AU - Kulenović, Alma Džubur

AU - Edenberg, Howard J.

AU - Evans, Alexandra

AU - Fabbri, Chiara

AU - Fani, Negar

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PY - 2024/5

Y1 - 2024/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85190650468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85190650468&partnerID=8YFLogxK

U2 - 10.1038/s41588-024-01707-9

DO - 10.1038/s41588-024-01707-9

M3 - Article

C2 - 38637617

AN - SCOPUS:85190650468

SN - 1061-4036

VL - 56

SP - 792

EP - 808

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

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

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