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

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Listed:
  • Jie Shen

    (Children’s Hospital of Soochow University
    Yale University School of Medicine)

  • Wander Valentim

    (Yale University School of Medicine
    Faculdade de Medicina da Universidade Federal de Minas Gerais)

  • Eleni Friligkou

    (Yale University School of Medicine
    VA Connecticut Healthcare Center)

  • Cassie Overstreet

    (Yale University School of Medicine
    VA Connecticut Healthcare Center)

  • Karmel W. Choi

    (Harvard T.H. Chan School of Public Health
    Massachusetts General Hospital)

  • Dora Koller

    (Yale University School of Medicine
    VA Connecticut Healthcare Center
    University of Barcelona)

  • Christopher J. O’Donnell

    (Veterans Affairs Boston Healthcare System)

  • Murray B. Stein

    (University of California San Diego
    Psychiatry Service
    School of Public Health)

  • Joel Gelernter

    (Yale University School of Medicine
    VA Connecticut Healthcare Center)

  • Haitao Lv

    (Children’s Hospital of Soochow University)

  • Ling Sun

    (Children’s Hospital of Soochow University)

  • Guido J. Falcone

    (Department of Neurology; Center for Brain and Mind Health Yale University New Haven CT USA, Yale University New Haven)

  • Renato Polimanti

    (Yale University School of Medicine
    VA Connecticut Healthcare Center
    Yale School of Public Health)

  • Gita A. Pathak

    (Yale University School of Medicine
    VA Connecticut Healthcare Center)

Abstract

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.

Suggested Citation

  • Jie Shen & Wander Valentim & Eleni Friligkou & Cassie Overstreet & Karmel W. Choi & Dora Koller & Christopher J. O’Donnell & Murray B. Stein & Joel Gelernter & Haitao Lv & Ling Sun & Guido J. Falcone , 2025. "Shared genetic architecture of posttraumatic stress disorder with cardiovascular imaging, risk, and diagnoses," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60487-w
    DOI: 10.1038/s41467-025-60487-w
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