# Genome-wide association summary statistics-based genetic mapping of brain functional and structural networks in Type 2 diabetes mellitus and its complications

Article · Chen L, Hsieh H, Cheng N, Xu Y

- Archive id: doi:10.1016/j.brainresbull.2026.112098
- Published: 2026-08-25
- Venue: Brain research bulletin
- DOI: https://doi.org/10.1016/j.brainresbull.2026.112098
- PMID: 42641768
- Citations: 0
- Source URL: https://doi.org/10.1016/j.brainresbull.2026.112098
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Connectomics & Brain Mapping](https://space-kitty.com/topics/connectomics)

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