Atlas of proteomic signatures of brain structure and its links to brain disorders
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.
Authors
- Fan Xu (ORCID: https://orcid.org/0000-0003-3910-5398)
- Jujiao Kang (ORCID: https://orcid.org/0000-0002-4489-7281)
- Wei Cheng (ORCID: https://orcid.org/0000-0003-1118-1743)
- Qing Ma (ORCID: https://orcid.org/0000-0002-5625-1330)
- Yong He (ORCID: https://orcid.org/0000-0002-7039-2850)
- Yuchao Jiang (ORCID: https://orcid.org/0000-0001-7012-0559)
- Jia You (ORCID: https://orcid.org/0000-0002-7079-8041)
- Chun Shen (ORCID: https://orcid.org/0000-0002-6677-4784)
- Linbo Wang (ORCID: https://orcid.org/0000-0002-6982-103X)
- Yujie Zhao (ORCID: https://orcid.org/0000-0002-7028-2408)
- Bang‐Sheng Wu (ORCID: https://orcid.org/0000-0002-8807-6354)
- Wei Zhang (ORCID: https://orcid.org/0000-0002-8208-3342)
- Bei Zhang (ORCID: https://orcid.org/0000-0003-0845-7534)
- Zeyu Li (ORCID: https://orcid.org/0000-0002-4413-7581)
- Yuzhu Li (ORCID: https://orcid.org/0000-0003-4231-6487)
- Meiyun Wang (ORCID: https://orcid.org/0000-0003-4454-5005)
- Weikang Gong (ORCID: https://orcid.org/0000-0002-5387-4428)
- Neil Roberts (ORCID: https://orcid.org/0000-0001-5538-8653)
- Jin‐Tai Yu (ORCID: https://orcid.org/0000-0002-2532-383X)
- Peng Ren
- Xiao‐He Hou
Institutions
- Qingdao University (CN)
- Fudan University (CN)
- Beijing Normal University (CN)
- MRC Centre for Regenerative Medicine (GB)
- MRC Centre for Reproductive Health (GB)
- Qingdao Municipal Hospital (CN)
- Henan Provincial People's Hospital (CN)
- Institute of Mechanics (CN)
- Huashan Hospital (CN)
- Shanghai Center for Brain Science and Brain-Inspired Technology (CN)
- State Key Laboratory of Medical Neurobiology
Publication Details
- Journal
- Nature Communications
- Published
- 2025-06-02
- DOI
- https://doi.org/10.1038/s41467-025-60185-7
- Citations
- 1
- Primary Topic
- Bioinformatics and Genomic Networks
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- National Natural Science Foundation of China
- Fudan University
- Huashan Hospital
- Higher Education Discipline Innovation Project
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Human Genome Research Institute
- NIH Office of the Director
- National Cancer Institute
- National Institute of Neurological Disorders and Stroke
- Common Fund