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Atlas of proteomic signatures of brain structure and its links to brain disorders

Author

Listed:
  • Peng Ren

    (Fudan University
    Fudan University
    Ministry of Education)

  • Xiao-He Hou

    (Fudan University
    Fudan University
    Ministry of Education
    University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital))

  • Zeyu Li

    (Fudan University
    Fudan University
    Ministry of Education)

  • Jia You

    (Fudan University
    Fudan University
    Ministry of Education)

  • Yuzhu Li

    (Fudan University
    Fudan University
    Ministry of Education)

  • Wei Zhang

    (Fudan University
    Fudan University
    Ministry of Education)

  • Weikang Gong

    (Fudan University)

  • Bei Zhang

    (Fudan University
    Fudan University
    Ministry of Education)

  • Bangsheng Wu

    (Fudan University
    Fudan University)

  • Linbo Wang

    (Fudan University
    Fudan University
    Ministry of Education)

  • Chun Shen

    (Fudan University
    Fudan University
    Ministry of Education)

  • Yujie Zhao

    (Fudan University
    Fudan University
    Ministry of Education)

  • Qing Ma

    (Fudan University
    Fudan University
    Ministry of Education)

  • Jujiao Kang

    (Fudan University
    Fudan University
    Ministry of Education)

  • Yuchao Jiang

    (Fudan University
    Fudan University
    Ministry of Education)

  • Neil Roberts

    (University of Edinburgh)

  • Fan Xu

    (Fudan University)

  • Yong He

    (Beijing Normal University
    Beijing Normal University)

  • Jin-Tai Yu

    (Fudan University
    Fudan University)

  • Meiyun Wang

    (Henan Provincial People’s Hospital & Zhengzhou University People’s Hospital)

  • Wei Cheng

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

Abstract

Individual variation in brain structure influences deterioration due to disease and comprehensive profiling of the associated proteomic signature advances mechanistic understanding. Here, using data from 4997 UK Biobank participants, we analyzed the associations between 2920 plasma proteins and 272 neuroimaging-derived brain structure measures. We identified 5358 associations between 1143 proteins and 256 brain structure measures, with NCAN and LEP proteins showing the most associations. Functional enrichment implicated these proteins in neurogenesis, immune/apoptotic processes and neurons. Furthermore, bidirectional Mendelian randomization revealed 33 associations between 32 proteins and 23 brain structure measures, and 21 associations between nine brain structure associated proteins and ten brain disorders. Moreover, the significant associations between the identified proteins and mental health were mediated by brain volume and surface area. In summary, this study generates a comprehensive atlas mapping the patterns of association between proteome and brain structure, highlighting their potential value for studying brain disorders.

Suggested Citation

  • Peng Ren & Xiao-He Hou & Zeyu Li & Jia You & Yuzhu Li & Wei Zhang & Weikang Gong & Bei Zhang & Bangsheng Wu & Linbo Wang & Chun Shen & Yujie Zhao & Qing Ma & Jujiao Kang & Yuchao Jiang & Neil Roberts , 2025. "Atlas of proteomic signatures of brain structure and its links to brain disorders," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60185-7
    DOI: 10.1038/s41467-025-60185-7
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