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Trans-ethnic estimation and implications of genetic impact on continuous glycemic profiles.

Overview

Authors: Evan Yi-Wen Yu1,2,3, Hui-Ying Ren1, Xinxiu Liang3, Yue Xi4, Menglei Shuai3, Zelei Miao3,5, Fengzhe Xu3,5, Ke Zhang3, Luqi Shen3,5, Hui Xia6, Miranda T Schram7,8,9, Marleen van Greevenbroek7,8, Bastiaan E de Galan7,8,10, Carla J H van der Kallen7,8, David E J Linden11, Gabriëlla A M Blokland11,12, Ilja C W Arts13, Tos T J M Berendschot14, Yan Yan4, Yuanqing Fu3,5, Anke Wesselius2,15, Yuming Chen4, Ju-Sheng Zheng3,5,16
ORCID iDs: Evan Yi-Wen Yu, Menglei Shuai, Marleen van Greevenbroek, Carla J H van der Kallen, Gabriëlla A M Blokland, Tos T J M Berendschot, Yuanqing Fu, Yuming Chen, Ju-Sheng Zheng
16 affiliations
  1. Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, Nanjing, Jiangsu China
  2. Department of Epidemiology, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands
  3. Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang China
  4. Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, Guangdong China
  5. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang China
  6. Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, Jiangsu China
  7. Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
  8. Department of Internal Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands
  9. Heart and Vascular Centre, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands
  10. Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
  11. Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Institute (MHeNs), Maastricht University, Maastricht, The Netherlands
  12. Psychiatric and Neurodevelopmental Genetics Unit, Centre for Genomic Medicine, and Department of Psychiatry, Massachusetts General Hospital, Boston, MA USA
  13. Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands
  14. University Eye Clinic Maastricht, MUMC+, Maastricht, The Netherlands
  15. School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
  16. Research Centre for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, Zhejiang China
Institutions: Westlake University (China); Maastricht University (Netherlands); Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine (China); Care and Public Health Research Institute (Netherlands); Southeast University (China); Sun Yat-sen University (China); Maastricht University Medical Centre (Netherlands); Radboud University Medical Center (Netherlands); Massachusetts General Hospital (United States)
Journal: Cell discovery, volume 12, issue 1, article 40
Dates: received 15 July 2025; accepted 12 April 2026; published online 4 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41421-026-00897-2 · PMID 42243095 · PMCID PMC13237324 · OpenAlex W7163574597
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: genetics / omics (modality), human (organism), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Machine learning, Preprocessing, Connectivity, fMRI & imaging
Keywords: Genome-wide association studies, Bioinformatics
Topic: Genetic Associations and Epidemiology (Genetics, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National Natural Science Foundation of China (National Science Foundation of China) (82204033, 92374112)
Citations: not cited yet (Europe PMC); 92 references in the paper

Abstract

The genetic architecture of glycemic dynamic metrics derived from continuous-glucose monitoring (CGM) across different populations remains poorly understood. Here, we conducted a trans-ethnic genome-wide association study (GWAS) meta-analysis of 20 CGM-derived glycemic traits, building upon a previously established European-ancestry CGM dataset and extending it through the inclusion of additional cohorts, in up to 9677 individuals originating from 2051 Chinese, 901 Dutch, and 6725 Israelis. Across 20 glycemic traits, we identified 18 genome-wide significant associations, of which 9 met study-wide significance, and three variants were novel. These variants indicated a shared genetic basis for continuous glycemic regulation and exhibited consistent patterns with those of sequential fingerstick glucose tests. Our findings further demonstrated that the identified genetic variants were enriched in pathways related to the nervous system. These findings were further supported by observed associations with brain magnetic resonance imaging (MRI) metrics, high CGM-related gene expression and co-regulation of quantitative trait loci in brain tissues. Additionally, we observed a positive relationship between genetic liability for the coefficient of variation (CV) and total cholesterol and a bi-directional putative causal relationship between hyperglycemia and type 1 diabetes across trans-ethnic populations. Moreover, we established a polygenic risk score (PRS) for additional participants and reported that certain glycemic traits were significantly associated with the risk of diabetes or pre-diabetes. These variants constituting the PRS demonstrated high transferability across general populations and pregnant women. Overall, our study yields unique insights into the high trans-ethnic and generalizable genetic architecture of CGM-derived glycemic profiles, supporting improved characterization of interindividual differences in glycemic dynamics and underscoring the potential for more personalized glucose management.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

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Data

No dataset and no data link were found in the paper.

Data availability

The summary statistics and datasets during this study are available upon reasonable request by bona fide researchers for specified scientific purposes via contacting the corresponding authors. Certain figures were created, adapted, and exported from BioRender.com (2024). Key analysis code is available from the corresponding authors upon reasonable request for specified scientific purposes.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 23 authors, 2 keywords, 1 funder, 87 references.

Cite

This paper

Yu, E. Y.-W., Ren, H.-Y., Liang, X., Xi, Y., Shuai, M., Miao, Z., Xu, F., Zhang, K., Shen, L., Xia, H., Schram, M. T., van Greevenbroek, M., de Galan, B. E., van der Kallen, C. J. H., Linden, D. E. J., Blokland, G. A. M., Arts, I. C. W., Berendschot, T. T. J. M., Yan, Y., . . . Zheng, J.-S. (2026). Trans-ethnic estimation and implications of genetic impact on continuous glycemic profiles. Cell discovery, 12(1), 40. https://doi.org/10.1038/s41421-026-00897-2

BibTeX

@article{yu2026trans,
author = {Yu, Evan Yi-Wen and Ren, Hui-Ying and Liang, Xinxiu and Xi, Yue and Shuai, Menglei and Miao, Zelei and Xu, Fengzhe and Zhang, Ke and Shen, Luqi and Xia, Hui and Schram, Miranda T and van Greevenbroek, Marleen and de Galan, Bastiaan E and van der Kallen, Carla J H and Linden, David E J and Blokland, Gabriëlla A M and Arts, Ilja C W and Berendschot, Tos T J M and Yan, Yan and Fu, Yuanqing and Wesselius, Anke and Chen, Yuming and Zheng, Ju-Sheng},
title = {{Trans-ethnic estimation and implications of genetic impact on continuous glycemic profiles}},
journal = {Cell discovery},
year = {2026},
month = jun,
volume = {12},
number = {1},
pages = {40},
publisher = {Nature Publishing Group},
issn = {2056-5968},
doi = {10.1038/s41421-026-00897-2},
url = {https://doi.org/10.1038/s41421-026-00897-2},
pmid = {42243095},
pmcid = {PMC13237324}
}

RIS

TY - JOUR
AU - Yu, Evan Yi-Wen
AU - Ren, Hui-Ying
AU - Liang, Xinxiu
AU - Xi, Yue
AU - Shuai, Menglei
AU - Miao, Zelei
AU - Xu, Fengzhe
AU - Zhang, Ke
AU - Shen, Luqi
AU - Xia, Hui
AU - Schram, Miranda T
AU - van Greevenbroek, Marleen
AU - de Galan, Bastiaan E
AU - van der Kallen, Carla J H
AU - Linden, David E J
AU - Blokland, Gabriëlla A M
AU - Arts, Ilja C W
AU - Berendschot, Tos T J M
AU - Yan, Yan
AU - Fu, Yuanqing
AU - Wesselius, Anke
AU - Chen, Yuming
AU - Zheng, Ju-Sheng
TI - Trans-ethnic estimation and implications of genetic impact on continuous glycemic profiles
T2 - Cell discovery
J2 - Cell Discov
PY - 2026
DA - 2026/06/04
VL - 12
IS - 1
SP - 40
SN - 2056-5968
PB - Nature Publishing Group
DO - 10.1038/s41421-026-00897-2
UR - https://doi.org/10.1038/s41421-026-00897-2
LA - en
ER -

CSL-JSON

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