Polygenic risk score for predicting diabetic retinopathy in patients with type 2 diabetes: A twenty-year follow-up study

doi:10.4239/wjd.v16.i10.110138

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World Journal of Diabetes

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1948-9358

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

World J Diabetes. Oct 15, 2025; 16(10): 110138
Published online Oct 15, 2025. doi: 10.4239/wjd.v16.i10.110138

Polygenic risk score for predicting diabetic retinopathy in patients with type 2 diabetes: A twenty-year follow-up study

Yu-Chuen Huang, Wen-Ling Liao, Hui-Ju Lin, Yu-Te Huang, Ya-Wen Chang, Jai-Sing Yang, Angel L Weng, Fuu-Jen Tsai

Yu-Chuen Huang, Hui-Ju Lin, Fuu-Jen Tsai, School of Chinese Medicine, China Medical University, Taichung 404, Taiwan

Yu-Chuen Huang, Ya-Wen Chang, Jai-Sing Yang, Fuu-Jen Tsai, Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan

Wen-Ling Liao, Center for Personalized Medicine, China Medical University Hospital and Graduate Institute of Integrated Medicine, China Medical University, Taichung 404, Taiwan

Hui-Ju Lin, Yu-Te Huang, Department of Ophthalmology, China Medical University Hospital, Taichung 404, Taiwan

Angel L Weng, American School in Taichung, Taichung 406, Taiwan

Angel L Weng, Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, United States

Fuu-Jen Tsai, Department of Medical Genetics, China Medical University Hospital, Taichung 404, Taiwan

Fuu-Jen Tsai, Division of Pediatric Genetics, Endocrinology and Metabolism, Children’s Hospital of China Medical University, Taichung 404, Taiwan

Co-first authors: Yu-Chuen Huang and Wen-Ling Liao.

Author contributions: Huang YC and Liao WL wrote the manuscript, and made equal contributions as co-first authors; Lin HJ, Huang YT, Chang YW, Yang JS, and Weng AL performed the research; Tsai FJ edited the manuscript. All authors have read and agreed to the published version of the manuscript.

Supported by China Medical University Hospital, No. DMR-113-105.

Institutional review board statement: The study was reviewed and approved by the Ethics Committee of China Medical University Hospital, No. CMUH111-REC1-176.

Informed consent statement: Written informed consent was obtained from all participants.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: No additional data are available.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Fuu-Jen Tsai, MD, PhD, Department of Medical Research, China Medical University Hospital, China Medical University, No. 2 Yuh-Der Road, Taichung 404, Taiwan. 000704@tool.caaumed.org.tw

Received: May 30, 2025
Revised: June 26, 2025
Accepted: September 18, 2025
Published online: October 15, 2025
Processing time: 139 Days and 0.9 Hours

Abstract

BACKGROUND

Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults, with an increasing prevalence due to the global burden of diabetes.

AIM

To develop a polygenic risk score (PRS) to identify high-risk groups for DR and evaluate its severity in patients with type 2 diabetes (T2D).

METHODS

This population-based study included 13335 patients with T2D, comprising 7295 patients with DR and 6040 without DR. Genetic data, duration of DR diagnosis, body mass index, systolic blood pressure, diastolic blood pressure, and glycated hemoglobin A1c levels were obtained from the study population. The PRS was constructed from a genome-wide association study conducted in a Taiwanese Han population. Electronic medical records were used to track patients with T2D and analyze the associations between PRS, timing of DR diagnosis, and therapeutic interventions. The hazard ratio (HR) of PRS for DR development and severity was estimated using multivariate Cox proportional hazards regression.

RESULTS

The results demonstrated that patients with T2D in the top PRS decile had a 1.21-fold greater risk of developing DR [HR = 1.21; 95% confidence interval (CI): 1.01-1.45; P = 0.041] over a 20-year follow-up period. Among patients with DR, those in the highest PRS decile exhibited a 4.81-fold increased risk of requiring more than four laser treatments (HR = 4.81; 95%CI: 1.40-16.5; P = 0.012) and a 1.38-fold increased risk of undergoing vitreoretinal surgery (HR = 1.38; 95%CI: 1.01-1.90; P = 0.044).

CONCLUSION

Patients with T2D with a higher PRS are at increased risk of developing DR and may experience more severe forms of the disease.

Keywords: Single nucleotide polymorphisms; Genome-wide association study; Polygenic risk score; Type 2 diabetes; Diabetic retinopathy

Core Tip: This population-based study developed a polygenic risk score (PRS) to assess diabetic retinopathy (DR) risk in patients with type 2 diabetes. Findings show that individuals with higher PRS are more likely to develop DR, including severe forms, over a 20-year period. Our study highlights the genetic basis of DR and introduces a potential tool for risk stratification and personalized screening in patients with type 2 diabetes. The PRS may help identify high-risk patients who could benefit from more frequent ophthalmological assessments and earlier intervention.