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

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, Fan Xu, Yong He, Jin-Tai Yu (), Meiyun Wang () and Wei Cheng ()
Additional contact information
Peng Ren: Fudan University
Xiao-He Hou: Fudan University
Zeyu Li: Fudan University
Jia You: Fudan University
Yuzhu Li: Fudan University
Wei Zhang: Fudan University
Weikang Gong: Fudan University
Bei Zhang: Fudan University
Bangsheng Wu: Fudan University
Linbo Wang: Fudan University
Chun Shen: Fudan University
Yujie Zhao: Fudan University
Qing Ma: Fudan University
Jujiao Kang: Fudan University
Yuchao Jiang: Fudan University
Neil Roberts: University of Edinburgh
Fan Xu: Fudan University
Yong He: Beijing Normal University
Jin-Tai Yu: Fudan University
Meiyun Wang: Henan Provincial People’s Hospital & Zhengzhou University People’s Hospital
Wei Cheng: Fudan University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60185-7

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