{"id":"doi:10.1016/j.brainresbull.2026.112098","kind":"article","title":"Genome-wide association summary statistics-based genetic mapping of brain functional and structural networks in Type 2 diabetes mellitus and its complications","authors":["Chen L","Hsieh H","Cheng N","Xu Y"],"author_count":4,"year":2026,"published":"2026-08-25","venue":"Brain research bulletin","cited_by":0,"doi":"10.1016/j.brainresbull.2026.112098","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.brainresbull.2026.112098","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.brainresbull.2026.112098","updated":null,"pmid":"42641768","pmcid":null,"openalex_id":null,"pdf_url":null,"abstract":"The disruptions in brain networks have been consistently observed in type 2 diabetes mellitus (T2DM) and complications. However, the causal effects and direction between these factors have yet to be elucidated. We conducted a two-sample bidirectional MR investigation supported by multiple sensitivity analyses. The study incorporated large-scale brain functional/structural network phenotypes from UK Biobank participants, while data for T2DM and related complications were provided by the FinnGen biobank. This dual-source approach ensured a rigorous evaluation of the causal interplay between neural traits and metabolic health. The forward MR analyses revealed two resting-state functional phenotypes and three white matter structural phenotypes that are genetically linked to a higher or lower risk of T2DM, all robust to global FDR correction (q < 0.05). Notably, the connectivity in default mode/Central executive and salience networks were associated with increased risk of T2DM (OR = 1.355, 95% CI = 1.217-1.510, P = 3.40 ×10 -8 , global FDR q < 0.05). Reverse MR analysis revealed that the genetically predisposed higher risk of diabetic maculopathy was associated with increased salience network connectivity (global FDR q < 0.05). Our results reveal significant causal associations between connectome phenotypes and T2DM, shedding light on the neural drivers of diabetic pathologies. While these findings broaden our understanding of the brain-T2DM interaction mechanism, subsequent longitudinal research is required to substantiate their relevance in a clinical setting.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Genome-wide association summary statistics-based genetic mapping of brain functional and structural networks in Type 2 diabetes mellitus and its complications\" by Chen L, Hsieh H, Cheng N et al., https://doi.org/10.1016/j.brainresbull.2026.112098, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"connectomics","name":"Connectomics & Brain Mapping","domain_slug":"neuroscience"}],"cited_in_dossiers":[]}