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Genetic associations of protein-coding variants in venous thromboembolism

Author

Listed:
  • Xiao-Yu He

    (Fudan University)

  • Bang-Sheng Wu

    (Fudan University)

  • Liu Yang

    (Fudan University)

  • Yu Guo

    (Fudan University)

  • Yue-Ting Deng

    (Fudan University)

  • Ze-Yu Li

    (Fudan University)

  • Chen-Jie Fei

    (Fudan University)

  • Wei-Shi Liu

    (Fudan University)

  • Yi-Jun Ge

    (Fudan University)

  • Jujiao Kang

    (Fudan University)

  • Jianfeng Feng

    (Fudan University
    Ministry of Education
    University of Warwick)

  • Wei Cheng

    (Fudan University
    Fudan University
    Ministry of Education
    University of Warwick)

  • Qiang Dong

    (Fudan University)

  • Jin-Tai Yu

    (Fudan University)

Abstract

Previous genetic studies of venous thromboembolism (VTE) have been largely limited to common variants, leaving the genetic determinants relatively incomplete. We performed an exome-wide association study of VTE among 14,723 cases and 334,315 controls. Fourteen known and four novel genes (SRSF6, PHPT1, CGN, and MAP3K2) were identified through protein-coding variants, with broad replication in the FinnGen cohort. Most genes we discovered exhibited the potential to predict future VTE events in longitudinal analysis. Notably, we provide evidence for the additive contribution of rare coding variants to known genome-wide polygenic risk in shaping VTE risk. The identified genes were enriched in pathways affecting coagulation and platelet activation, along with liver-specific expression. The pleiotropic effects of these genes indicated the potential involvement of coagulation factors, blood cell traits, liver function, and immunometabolic processes in VTE pathogenesis. In conclusion, our study unveils the valuable contribution of protein-coding variants in VTE etiology and sheds new light on its risk stratification.

Suggested Citation

  • Xiao-Yu He & Bang-Sheng Wu & Liu Yang & Yu Guo & Yue-Ting Deng & Ze-Yu Li & Chen-Jie Fei & Wei-Shi Liu & Yi-Jun Ge & Jujiao Kang & Jianfeng Feng & Wei Cheng & Qiang Dong & Jin-Tai Yu, 2024. "Genetic associations of protein-coding variants in venous thromboembolism," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47178-8
    DOI: 10.1038/s41467-024-47178-8
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    References listed on IDEAS

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