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Polygenic risk score and cluster-based analysis suggests links between type 2 diabetes and vascular dementia in the KARE study

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  • Wanqing Dong

    (and College of Clinical Medicine of Henan University of Science and Technology, The First Affiliated Hospital
    Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine
    Key Laboratory of Hereditary Rare Diseases of Health Commission of Henan Province
    Henan Key Laboratory of Rare Diseases)

  • Zijian Tian

    (Guangzhou National Laboratory
    Institute of Biophysics Chinese Academy of Sciences, National Laboratory of Biomacromolecules
    University of the Chinese Academy of Sciences, College of Life Sciences)

  • Jie Bai

    (Nankai University, College of Pharmacy
    Nankai University, State Key Laboratory of Medicinal Chemical Biology
    Nankai University, Frontiers Science Center for Cell Responses)

  • Benrui Wu

    (Guangzhou National Laboratory
    Institute of Biophysics Chinese Academy of Sciences, National Laboratory of Biomacromolecules
    University of the Chinese Academy of Sciences, College of Life Sciences)

  • Mengjie Zhao

    (Affiliated Kunshan Hospital of Jiangsu University, Department of General Practice
    Kunshan Biomedical Big Data Innovation Application Laboratory)

  • Yingyu Zhang

    (and College of Clinical Medicine of Henan University of Science and Technology, The First Affiliated Hospital)

  • Jian Shao

    (Guangzhou National Laboratory)

  • Tian Xie

    (Guangzhou National Laboratory)

  • Qian Li

    (Guangzhou National Laboratory)

  • Peng Wu

    (Nankai University, College of Pharmacy
    Nankai University, State Key Laboratory of Medicinal Chemical Biology
    Nankai University, Frontiers Science Center for Cell Responses)

  • Jingnan Xue

    (Nankai University, College of Pharmacy
    Nankai University, State Key Laboratory of Medicinal Chemical Biology
    Nankai University, Frontiers Science Center for Cell Responses)

  • Ying Chen

    (Guangzhou National Laboratory
    Guangzhou Medical University, College of Public Health)

  • Xiaozhou Zhou

    (Guangzhou National Laboratory)

  • Yuxuan Du

    (Guangzhou National Laboratory)

  • Shiteng Gao

    (Guangzhou National Laboratory
    Guangzhou Medical University, College of Public Health)

  • Haonan Pan

    (Guangzhou National Laboratory
    Guangzhou Medical University, College of Public Health)

  • Anjie Peng

    (Guangzhou National Laboratory
    Guangzhou Medical University, College of Public Health)

  • Ying Pan

    (Affiliated Kunshan Hospital of Jiangsu University, Department of General Practice
    Kunshan Biomedical Big Data Innovation Application Laboratory)

  • Kaixin Zhou

    (Guangzhou National Laboratory
    Guangzhou Medical University, College of Public Health)

  • Hongwei Jiang

    (and College of Clinical Medicine of Henan University of Science and Technology, The First Affiliated Hospital
    Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine
    Key Laboratory of Hereditary Rare Diseases of Health Commission of Henan Province
    Henan Key Laboratory of Rare Diseases)

Abstract

Type 2 diabetes is an established risk factor for dementia. However, how its genetic heterogeneity affects different dementia subtypes remains unclear. In this study, we investigate the associations between genetic risk of type 2 diabetes and dementia subtypes among 33,136 older Chinese adults from the KARE cohort. We find that a higher overall polygenic risk score for type 2 diabetes is significantly associated with an increased risk of vascular dementia, but not Alzheimer’s disease. Further analyses using cluster-specific partitioned polygenic score show that elevated genetic risk specific to the hyperinsulinemia pathway is strongly associated with increased incidence of vascular dementia. These findings highlight the potential role of insulin-related metabolic abnormalities in the pathogenesis of vascular dementia and provide genetic evidence to support the use of the hyperinsulinaemia pathway as a clinically relevant marker for early risk stratification and precision prevention strategies.

Suggested Citation

  • Wanqing Dong & Zijian Tian & Jie Bai & Benrui Wu & Mengjie Zhao & Yingyu Zhang & Jian Shao & Tian Xie & Qian Li & Peng Wu & Jingnan Xue & Ying Chen & Xiaozhou Zhou & Yuxuan Du & Shiteng Gao & Haonan P, 2025. "Polygenic risk score and cluster-based analysis suggests links between type 2 diabetes and vascular dementia in the KARE study," Nature Communications, Nature, vol. 16(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65252-7
    DOI: 10.1038/s41467-025-65252-7
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    References listed on IDEAS

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    1. Olivier Delaneau & Jean-François Zagury & Matthew R. Robinson & Jonathan L. Marchini & Emmanouil T. Dermitzakis, 2019. "Accurate, scalable and integrative haplotype estimation," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    2. Ken Suzuki & Konstantinos Hatzikotoulas & Lorraine Southam & Henry J. Taylor & Xianyong Yin & Kim M. Lorenz & Ravi Mandla & Alicia Huerta-Chagoya & Giorgio E. M. Melloni & Stavroula Kanoni & Nigel W. , 2024. "Genetic drivers of heterogeneity in type 2 diabetes pathophysiology," Nature, Nature, vol. 627(8003), pages 347-357, March.
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