Fig. 1: Workflow illustrating the integrative analysis pipeline.

A Neuroimaging meta-analyses were conducted to identify GMV alterations in T2DM and MDD, and to determine the overlapping regions of GMV reduction between the two conditions. B Shared genes were identified using conjFDR analysis applied to large-scale GWAS summary statistics for T2DM and MDD. Gene expression profiles were extracted from the AHBA database to construct the gene expression matrix. C Transcriptome-neuroimaging association analysis combined voxel-wise Z-values of GMV changes with the expression matrix of shared genes to identify genes associated with GMV alterations in each disorder and their overlap. D Expression-trait association analyses were used to prioritize shared genes, and functional validation was conducted through phenotypic profiling of knockout mouse models. AHBA allen human brain atlas, conjFDR conjunctional false discovery rate, GMV gray matter volume, HC healthy control, MDD major depression disorder, T2DM type 2 diabetes mellitus.