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.