School of Medicine Publications and Presentations
Document Type
Article
Publication Date
9-24-2025
Abstract
To better characterize the potential biological mechanisms underlying insulin resistance (IR) and dementia, we derive cross-population and population specific polygenic scores [PSs] for fasting insulin and IR-related partitioned PSs [pPSs]. We conduct a cross-sectional study of the associations of these genetic scores with neurological outcomes in >17k participants (36% men, mean age 55 yrs) from the Trans-Omics for Precision Medicine (TOPMed) program (50% Non-Hispanic White, 23% Black/African American, 21% Hispanic/Latino American, and 4% Asian American). We report significant negative associations (P < 0.002) of the cross-population (P = 1.3 × 10-5) and European (PEA = 3.0 × 10-8) fasting insulin PSs with total cranial volume, and of a metabolic syndrome European PS with general cognitive function (BEA = -0.13, PEA = 0.0002) and lateral ventricular volume (BEA = 0.09, PEA = 0.002). We identify suggestive negative associations (P < 0.007) of metabolic syndrome and obesity pPSs with general cognitive function, and of lipodystrophy pPSs with total cranial volume. A higher genetic predisposition to IR is associated with lower brain size, and a genetic predisposition to specific IR-related type 2 diabetes subtypes, such as metabolic syndrome and mechanisms of IR mediated through obesity and lipodystrophy, is potentially involved in cognitive decline.
Recommended Citation
Sarnowski, C., Zhang, Y., Ammous, F., Shade, L. M., DiCorpo, D., Jian, X., ... & TOPMed Neurocognitive working group Glahn David C. 23 24 25. (2025). Association of genetic scores related to insulin resistance with neurological outcomes in ancestrally diverse cohorts from the Trans-Omics for Precision Medicine (TOPMed) program. Communications biology, 8(1), 1352. https://doi.org/10.1038/s42003-025-08674-9
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Publication Title
Communications biology
DOI
10.1038/s42003-025-08674-9
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it.