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Large-scale whole-exome sequencing of neuropsychiatric diseases and traits in 350,770 adults

Author

Listed:
  • Yue-Ting Deng

    (Fudan University)

  • Bang-Sheng Wu

    (Fudan University)

  • Liu Yang

    (Fudan University)

  • Xiao-Yu He

    (Fudan University)

  • Ju-Jiao Kang

    (Fudan University
    Ministry of Education)

  • Wei-Shi Liu

    (Fudan University)

  • Ze-Yu Li

    (Fudan University
    Ministry of Education)

  • Xin-Rui Wu

    (Fudan University)

  • Ya-Ru Zhang

    (Fudan University)

  • Shi-Dong Chen

    (Fudan University)

  • Yi-Jun Ge

    (Fudan University)

  • Yu-Yuan Huang

    (Fudan University)

  • Jian-Feng Feng

    (Fudan University
    Ministry of Education
    University of Warwick)

  • Ying Zhu

    (Fudan University)

  • Qiang Dong

    (Fudan University)

  • Ying Mao

    (Huashan Hospital Fudan University)

  • Wei Cheng

    (Fudan University
    Fudan University
    Ministry of Education
    Zhejiang Normal University)

  • Jin-Tai Yu

    (Fudan University)

Abstract

While numerous genomic loci have been identified for neuropsychiatric conditions, the contribution of protein-coding variants has yet to be determined. Here we conducted a large-scale whole-exome-sequencing study to interrogate the impact of protein-coding variants on 46 neuropsychiatric diseases and 23 traits in 350,770 adults from the UK Biobank. Twenty new genes were associated with neuropsychiatric diseases through coding variants, among which 16 genes had impacts on the longitudinal risks of diseases. Thirty new genes were associated with neuropsychiatric traits, with SYNGAP1 showing pleiotropic effects across cognitive function domains. Pairwise estimation of genetic correlations at the coding-variant level highlighted shared genetic associations among pairs of neurodegenerative diseases and mental disorders. Lastly, a comprehensive multi-omics analysis suggested that alterations in brain structures, blood proteins and inflammation potentially contribute to the gene–phenotype linkages. Overall, our findings characterized a compendium of protein-coding variants for future research on the biology and therapeutics of neuropsychiatric phenotypes.

Suggested Citation

  • Yue-Ting Deng & Bang-Sheng Wu & Liu Yang & Xiao-Yu He & Ju-Jiao Kang & Wei-Shi Liu & Ze-Yu Li & Xin-Rui Wu & Ya-Ru Zhang & Shi-Dong Chen & Yi-Jun Ge & Yu-Yuan Huang & Jian-Feng Feng & Ying Zhu & Qiang, 2024. "Large-scale whole-exome sequencing of neuropsychiatric diseases and traits in 350,770 adults," Nature Human Behaviour, Nature, vol. 8(6), pages 1194-1208, June.
    • Handle: RePEc:nat:nathum:v:8:y:2024:i:6:d:10.1038_s41562-024-01861-4
    DOI: 10.1038/s41562-024-01861-4
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    Cited by:

    1. Thomas Vaissiere & Sheldon D. Michaelson & Thomas Creson & Jessie Goins & Daniel Fürth & Diana Balazsfi & Camilo Rojas & Randall Golovin & Konstantinos Meletis & Courtney A. Miller & Daniel O’Connor &, 2025. "Syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamics," Nature Communications, Nature, vol. 16(1), pages 1-23, December.

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