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Contribution of leukocyte telomere length to cardiovascular disease onset from genome-wide cross-trait analysis

Author

Listed:
  • Jun Qiao

    (Southern University of Science and Technology
    Shenzhen People’s Hospital (The First Affiliated Hospital of Southern University of Science and Technology)
    Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases)

  • Qian Wang

    (The Fifth Clinical Medical College of Shanxi Medical University)

  • Yuhui Zhao

    (Second Hospital of Shanxi Medical University)

  • Minjing Chang

    (Southern University of Science and Technology)

  • Shuo Sun

    (Southern Medical University)

  • Pengwei Zhang

    (Southern University of Science and Technology
    Shenzhen People’s Hospital (The First Affiliated Hospital of Southern University of Science and Technology)
    Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases)

  • Kaixin Yao

    (Second Hospital of Shanxi Medical University)

  • Miaoran Chen

    (Second Hospital of Shanxi Medical University)

  • Leilei Zheng

    (Second Hospital of Shanxi Medical University)

  • Xiaolong Xing

    (Second Hospital of Shanxi Medical University)

  • Liuyang Cai

    (Southern University of Science and Technology
    Shenzhen People’s Hospital (The First Affiliated Hospital of Southern University of Science and Technology)
    Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases)

  • Anil G. Jegga

    (University of Cincinnati College of Medicine
    University of Cincinnati College of Engineering
    University of Cincinnati)

  • Lei Jiang

    (Southern Medical University)

  • Siim Pauklin

    (Headington)

  • Rongjun Zou

    (Guangdong Provincial Hospital of Chinese Medicine
    State Key Laboratory of Dampness Syndrome of Chinese Medicine
    Guangdong Provincial Key Laboratory of TCM Emergency Research)

  • Yining Yang

    (People’s Hospital of Xinjiang Uygur Autonomous Region
    Xinjiang Key Laboratory of Cardiovascular Homeostasis and Regeneration Research)

  • Yuliang Feng

    (Southern University of Science and Technology
    Shenzhen People’s Hospital (The First Affiliated Hospital of Southern University of Science and Technology)
    Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases)

Abstract

Telomere shortening is a well-established marker of cellular aging and genomic instability. While the relationship between leukocyte telomere length and cardiovascular diseases has long been of interest, their genetic interplay remains incompletely understood. In this study, we observe substantial genetic overlap beyond genome-wide correlations and identify a potential causal relationship between leukocyte telomere length and coronary artery disease. Specifically, we discover 248 pleiotropic loci, 22 of which show strong evidence of colocalization. Some shared loci implicate multiple pleiotropic genes across different trait pairs, including ALDH2, ACAD10, TMEM116, SH2B3 (all at 12q24.12), TMED6 (16q22.1), SERPINF1 (17p13.3), and XPO7 (8p21.3). Functional analysis highlights key pathways involved in DNA biosynthesis and telomere maintenance. Notably, SH2B3 is validated through proteome-wide Mendelian randomization analysis, suggesting its potential as a therapeutic target. Here we report the shared genetic basis between leukocyte telomere length and cardiovascular diseases, providing valuable insights into future therapeutic developments.

Suggested Citation

  • Jun Qiao & Qian Wang & Yuhui Zhao & Minjing Chang & Shuo Sun & Pengwei Zhang & Kaixin Yao & Miaoran Chen & Leilei Zheng & Xiaolong Xing & Liuyang Cai & Anil G. Jegga & Lei Jiang & Siim Pauklin & Rongj, 2025. "Contribution of leukocyte telomere length to cardiovascular disease onset from genome-wide cross-trait analysis," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63707-5
    DOI: 10.1038/s41467-025-63707-5
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