ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1672403
This article is part of the Research TopicGenetic Mechanisms in Diabetes PathogenesisView all 5 articles
Genetic and Phenotypic Heterogeneity of Type 2 Diabetes Across Russian Ancestry Groups
Provisionally accepted
Ekaterina E Markelova1,2
Irina V Kononenko3Anatoliy Zubritskiy1,3Elizaveta Podshivalova3Alina Matrosova3
Evgeniya Plaksina3Saleem Mansour4Pavel Ahtyamov3,4Elena Shagimardanova5,6Gulnar R Vagapova7Nadezhda Maksimova8Liubov A Sydykova8Diana S Avzaletdinova9Tatiana V Morugova9Petimat M Dzhambetova10
Marina Shestakova3
Natalia Georgievna Mokrysheva3
Yulia A Medvedeva1,3*- 1Federal Center Research Fundamentals of Biotechnology (RAS), Moscow, Russia
- 2MSU Institute for Artificial Intelligence, Lomonosov Moscow State University, Moscow, Russia
- 3Endocrinology Research Center, Moscow, Russia
- 4Moscow Center for Advanced Studies, Moscow, Russia
- 5Skolkovo Institute of Science and Technology, Moscow, Russia
- 6Life Improvement by Future Technologies (LIFT) Center,, Moscow, Russia
- 7Kazan State Medical Academy, Kazan, Russia
- 8North-Eastern Federal University, Yakutsk, Russia
- 9Bashkir State Medical University, Ufa, Russia
- 10Chechen State University named after A. A. Kadyrov, Grozny, Russia
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Type 2 diabetes mellitus (T2D) is a highly polygenic disease involving multiple biological pathways during its progression. Genetic ancestry may shape the predominant biological pathways driving T2D. Understanding how genetic background shapes T2D risk is crucial for developing personalized prevention and treatment strategies. The primary objective of this study was to analyze ancestry-specific differences in the mechanisms underlying T2D and to assess the prevalence of 1 T2D-associated genetic clusters, reflecting biological mechanisms underlying T2D onset and progression, in individuals from distinct ancestry groups of Russia – Chechens, Tatars, and Yakuts. We applied previously developed polygenic scores to assess T2D genetic clusters and their prevalence in ancestry groups, evaluating clinical risk factors across ancestry groups. Cluster-specific polygenic scores varied significantly between populations of different ancestries. Yakuts exhibited higher scores for β-cell dysfunction, hyper-insulin secretion, and changes in lipid metabolism, while Chechens and Tatars showed higher scores for obesity-related mechanisms. We conclude that the predominant mechanisms underlying T2D can differ across populations, and this should be accounted for in public health recommendations and medicine.
Keywords: type 2 diabetes, genotyping, ancestry, Risk scores, Genetic mechanism, Russian population, Genetic association, beta cell dysfunction
Received: 24 Jul 2025; Accepted: 25 Aug 2025.
Copyright: © 2025 Markelova, Kononenko, Zubritskiy, Podshivalova, Matrosova, Plaksina, Mansour, Ahtyamov, Shagimardanova, Vagapova, Maksimova, Sydykova, Avzaletdinova, Morugova, Dzhambetova, Shestakova, Mokrysheva and Medvedeva. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yulia A Medvedeva, Federal Center Research Fundamentals of Biotechnology (RAS), Moscow, Russia
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.