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

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; Renato Polimanti; Gita A. Pathak; Thomas Werge; Derrick Silove; Merete Nordentoft; Karen Inge Karstoft; Posttraumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium

doi:10.1038/s41467-025-60487-w

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

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, Renato Polimanti^*, Gita A. Pathak^*, Thomas Werge (Medlem af forfattergruppering), Derrick Silove (Medlem af forfattergruppering), Merete Nordentoft (Medlem af forfattergruppering), Karen Inge Karstoft (Medlem af forfattergruppering), Posttraumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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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.

Originalsprog	Engelsk
Artikelnummer	5631
Tidsskrift	Nature Communications
Vol/bind	16
Udgave nummer	1
Antal sider	17
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-025-60487-w
Status	Udgivet - 2025

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Publisher Copyright:
© The Author(s) 2025.

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Shen, J., Valentim, W., Friligkou, E., Overstreet, C., Choi, K. W., Koller, D., O’Donnell, C. J., Stein, M. B., Gelernter, J., Lv, H., Sun, L., Falcone, G. J., Polimanti, R., Pathak, G. A., Werge, T., Silove, D., Nordentoft, M., Karstoft, K. I., & Posttraumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium (2025). Shared genetic architecture of posttraumatic stress disorder with cardiovascular imaging, risk, and diagnoses. Nature Communications, 16(1), Artikel 5631. https://doi.org/10.1038/s41467-025-60487-w

Shen, J, Valentim, W, Friligkou, E, Overstreet, C, Choi, KW, Koller, D, O’Donnell, CJ, Stein, MB, Gelernter, J, Lv, H, Sun, L, Falcone, GJ, Polimanti, R, Pathak, GA, Werge, T , Silove, D , Nordentoft, M , Karstoft, KI & Posttraumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium 2025, 'Shared genetic architecture of posttraumatic stress disorder with cardiovascular imaging, risk, and diagnoses', Nature Communications, bind 16, nr. 1, 5631. https://doi.org/10.1038/s41467-025-60487-w

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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{\textquoteright}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.",

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AU - Shen, Jie

AU - Valentim, Wander

AU - Friligkou, Eleni

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AU - O’Donnell, Christopher J.

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AU - Gelernter, Joel

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AU - Falcone, Guido J.

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AU - Pathak, Gita A.

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AB - 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.

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