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Unraveling the causal genes and transcriptomic determinants of human telomere length

Author

Listed:
  • Ying Chang

    (Nankai University)

  • Yao Zhou

    (Tianjin Medical University)

  • Junrui Zhou

    (Tianjin Medical University
    Shanghai Jiaotong University)

  • Wen Li

    (Nankai University)

  • Jiasong Cao

    (Nankai University)

  • Yaqing Jing

    (Tianjin Medical University)

  • Shan Zhang

    (Tianjin Medical University)

  • Yongmei Shen

    (Nankai University)

  • Qimei Lin

    (Nankai University)

  • Xutong Fan

    (Tianjin Medical University)

  • Hongxi Yang

    (Tianjin Medical University
    Tianjin Medical University)

  • Xiaobao Dong

    (Tianjin Medical University)

  • Shijie Zhang

    (Tianjin Medical University)

  • Xianfu Yi

    (Tianjin Medical University)

  • Ling Shuai

    (Nankai University)

  • Lei Shi

    (Tianjin Medical University)

  • Zhe Liu

    (Tianjin Medical University)

  • Jie Yang

    (Tianjin Medical University)

  • Xin Ma

    (Jiangnan University)

  • Jihui Hao

    (Tianjin Medical University Cancer Institute and Hospital)

  • Kexin Chen

    (Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University)

  • Mulin Jun Li

    (Tianjin Medical University
    Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University)

  • Feng Wang

    (Tianjin Medical University
    Tianjin Medical University School of Stomatology, Tianjin Medical University
    Tianjin Medical University General Hospital; Tianjin Geriatrics Institute)

  • Dandan Huang

    (Tianjin Medical University
    Jiangnan University)

Abstract

Telomere length (TL) shortening is a pivotal indicator of biological aging and is associated with many human diseases. The genetic determinates of human TL have been widely investigated, however, most existing studies were conducted based on adult tissues which are heavily influenced by lifetime exposure. Based on the analyses of terminal restriction fragment (TRF) length of telomere, individual genotypes, and gene expressions on 166 healthy placental tissues, we systematically interrogate TL-modulated genes and their potential functions. We discover that the TL in the placenta is comparatively longer than in other adult tissues, but exhibiting an intra-tissue homogeneity. Trans-ancestral TL genome-wide association studies (GWASs) on 644,553 individuals identify 20 newly discovered genetic associations and provide increased polygenic determination of human TL. Next, we integrate the powerful TL GWAS with placental expression quantitative trait locus (eQTL) mapping to prioritize 23 likely causal genes, among which 4 are functionally validated, including MMUT, RRM1, KIAA1429, and YWHAZ. Finally, modeling transcriptomic signatures and TRF-based TL improve the prediction performance of human TL. This study deepens our understanding of causal genes and transcriptomic determinants of human TL, promoting the mechanistic research on fine-grained TL regulation.

Suggested Citation

  • Ying Chang & Yao Zhou & Junrui Zhou & Wen Li & Jiasong Cao & Yaqing Jing & Shan Zhang & Yongmei Shen & Qimei Lin & Xutong Fan & Hongxi Yang & Xiaobao Dong & Shijie Zhang & Xianfu Yi & Ling Shuai & Lei, 2023. "Unraveling the causal genes and transcriptomic determinants of human telomere length," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44355-z
    DOI: 10.1038/s41467-023-44355-z
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    References listed on IDEAS

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