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Exome sequencing identifies genes associated with sleep-related traits

Author

Listed:
  • Chen-Jie Fei

    (Fudan University)

  • Ze-Yu Li

    (Fudan University
    Fudan University, Ministry of Education)

  • Jing Ning

    (Fudan University)

  • Liu Yang

    (Fudan University)

  • Bang-Sheng Wu

    (Fudan University)

  • Ju-Jiao Kang

    (Fudan University
    Fudan University, Ministry of Education)

  • Wei-Shi Liu

    (Fudan University)

  • Xiao-Yu He

    (Fudan University)

  • Jia You

    (Fudan University
    Fudan University, Ministry of Education)

  • Shi-Dong Chen

    (Fudan University)

  • Huan Yu

    (Fudan University)

  • Zhi-Li Huang

    (Fudan University)

  • Jian-Feng Feng

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

  • Jin-Tai Yu

    (Fudan University)

  • Wei Cheng

    (Fudan University
    Fudan University
    Fudan University, Ministry of Education)

Abstract

Sleep is vital for human health and has a moderate heritability. Previous genome-wide association studies have limitations in capturing the role of rare genetic variants in sleep-related traits. Here we conducted a large-scale exome-wide association study of eight sleep-related traits (sleep duration, insomnia symptoms, chronotype, daytime sleepiness, daytime napping, ease of getting up in the morning, snoring and sleep apnoea) among 450,000 participants from UK Biobank. We identified 22 new genes associated with chronotype (ADGRL4, COL6A3, CLK4 and KRTAP3-3), daytime sleepiness (ST3GAL1 and ANKRD12), daytime napping (PLEKHM1, ANKRD12 and ZBTB21), snoring (WDR59) and sleep apnoea (13 genes). Notably, 20 of these genes were confirmed to be significantly associated with sleep disorders in the FinnGen cohort. Enrichment analysis revealed that these discovered genes were enriched in circadian rhythm and central nervous system neurons. Phenotypic association analysis showed that ANKRD12 was associated with cognition and inflammatory traits. Our results demonstrate the value of large-scale whole-exome analysis in understanding the genetic architecture of sleep-related traits and potential biological mechanisms.

Suggested Citation

  • Chen-Jie Fei & Ze-Yu Li & Jing Ning & Liu Yang & Bang-Sheng Wu & Ju-Jiao Kang & Wei-Shi Liu & Xiao-Yu He & Jia You & Shi-Dong Chen & Huan Yu & Zhi-Li Huang & Jian-Feng Feng & Jin-Tai Yu & Wei Cheng, 2024. "Exome sequencing identifies genes associated with sleep-related traits," Nature Human Behaviour, Nature, vol. 8(3), pages 576-589, March.
    • Handle: RePEc:nat:nathum:v:8:y:2024:i:3:d:10.1038_s41562-023-01785-5
    DOI: 10.1038/s41562-023-01785-5
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