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<p>Patients with post-traumatic stress disorder face increased cardiovascular risk. This study examines shared genetic regions between post-traumatic stress disorder and 246 cardiovascular conditions across electronic health records, 82 cardiac imaging, and health behaviors defined by Life’s Essential 8. Post-traumatic stress disorder is genetically correlated with cardiovascular diagnoses in 33 regions, imaging traits in 4 regions, and health behaviors in 44 regions. Potentially shared causal variants between post-traumatic stress disorder and 17 cardiovascular conditions were observed in 11 regions. Subsequent observational analysis in AllofUS cohort showed post-traumatic stress disorder is associated with 13 diagnoses even after accounting for socioeconomic factors and depression. Genetically regulated proteome expression in brain and blood tissues identified 33 blood and 122 brain genes shared between the two conditions, revealing neuronal, immune, metabolic, and calcium-related mechanisms, with several genes as targets for existing drugs. These findings exhibit shared risk loci and genes are involved in tissue-specific mechanisms.</p>

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Shared genetic architecture of posttraumatic stress disorder with cardiovascular imaging, risk, and diagnoses

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Jie Shen,
  • Wander Valentim,
  • Eleni Friligkou,
  • Cassie Overstreet,
  • Karmel W. Choi,
  • Dora Koller,
  • Christopher J. O’Donnell,
  • Murray B. Stein,
  • Joel Gelernter,
  • Caroline M. Nievergelt,
  • Adam X. Maihofer,
  • Elizabeth G. Atkinson,
  • Chia-Yen Chen,
  • Jonathan RI Coleman,
  • Nikolaos P. Daskalakis,
  • Laramie E. Duncan,
  • Cindy Aaronson,
  • Ananda B. Amstadter,
  • Soren B. Andersen,
  • Ole A. Andreassen,
  • Paul A. Arbisi,
  • Allison E. Ashley-Koch,
  • S. Bryn Austin,
  • Esmina Avdibegoviç,
  • Dragan Babic,
  • 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,
  • Terri deRoon-Cassini,
  • Frank Desarnaud,
  • Christopher P. DiPietro,
  • Seth G. Disner,
  • Anna R. Docherty,
  • Katharina Domschke,
  • Grete Dyb,
  • Alma Dzubur Kulenovic,
  • 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,
  • Elbert Geuze,
  • Charles F. Gillespie,
  • Aferdita Goci,
  • Slavina B. Goleva,
  • Scott D. Gordon,
  • Lana Ruvolo Grasser,
  • Camila Guindalini,
  • Magali Haas,
  • Saskia Hagenaars,
  • Michael A. Hauser,
  • Andrew C. Heath,
  • Sian MJ Hemmings,
  • Victor Hesselbrock,
  • Ian B. Hickie,
  • Kelleigh Hogan,
  • David Michael Hougaard,
  • Hailiang Huang,
  • Laura M. Huckins,
  • Kristian Hveem,
  • Miro Jakovljevic,
  • 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,
  • 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,
  • Barbara O. Rothbaum,
  • Alex 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,
  • Leigh Luella van den Heuvel,
  • Miranda Van Hooff,
  • Sanne JH van Rooij,
  • Eric Vermetten,
  • Christiaan H. Vinkers,
  • Joanne Voisey,
  • Zhewu Wang,
  • Yunpeng Wang,
  • Monika Waszczuk,
  • Heike Weber,
  • Frank R. Wendt,
  • Thomas Werge,
  • Michelle A. Williams,
  • Douglas E. Williamson,
  • Bendik S. Winsvold,
  • Sherry Winternitz,
  • Erika J. Wolf,
  • Christiane Wolf,
  • Yan Xia,
  • Ying Xiong,
  • Rachel Yehuda,
  • Ross McD Young,
  • Keith A. Young,
  • Clement C. Zai,
  • Gwyneth C. Zai,
  • Mark Zervas,
  • Hongyu Zhao,
  • Lori A. Zoellner,
  • John-Anker Zwart,
  • Kerry J. Ressler,
  • Karestan C. Koenen,
  • Haitao Lv,
  • Ling Sun,
  • Guido J. Falcone,
  • Renato Polimanti,
  • Gita A. Pathak

摘要

Patients with post-traumatic stress disorder face increased cardiovascular risk. This study examines shared genetic regions between post-traumatic stress disorder and 246 cardiovascular conditions across electronic health records, 82 cardiac imaging, and health behaviors defined by Life’s Essential 8. Post-traumatic stress disorder is genetically correlated with cardiovascular diagnoses in 33 regions, imaging traits in 4 regions, and health behaviors in 44 regions. Potentially shared causal variants between post-traumatic stress disorder and 17 cardiovascular conditions were observed in 11 regions. Subsequent observational analysis in AllofUS cohort showed post-traumatic stress disorder is associated with 13 diagnoses even after accounting for socioeconomic factors and depression. Genetically regulated proteome expression in brain and blood tissues identified 33 blood and 122 brain genes shared between the two conditions, revealing neuronal, immune, metabolic, and calcium-related mechanisms, with several genes as targets for existing drugs. These findings exhibit shared risk loci and genes are involved in tissue-specific mechanisms.