Pathway insights and predictive modeling for type 2 diabetes using polygenic risk scores

• Published in: Scientific reports Vol. 15; no. 1; pp. 28956 - 11
• Main Authors: Liao, Wen-Ling, Yang, Jai-Sing, Liu, Ting-Yuan, Lu, Hsing-Fang, Chang, Ya-Wen, Tsai, Fuu-Jen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.08.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/721; 692/53/2423; 692/699/2743; Aged; Case-Control Studies; Codes; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Disease; Electronic medical records; Erectile dysfunction; Female; Genetic Predisposition to Disease; Genetic Risk Score; Genome-wide association studies; Genome-Wide Association Study; Genomes; Global health; Humanities and Social Sciences; Humans; Hypertension; Male; Middle Aged; multidisciplinary; Multifactorial Inheritance; Pathway analysis; PheWAS; Polygenic risk score; Polymorphism, Single Nucleotide; Prediction models; Public health; Quality control; Retinopathy; Risk Assessment; Risk Factors; Science; Science (multidisciplinary); Score system; Taiwan - epidemiology; Type 2 diabetes; Wnt protein; β-Catenin; Taiwan; United States > US; Type 2 diabetes; Polygenic risk score; PheWAS; Pathway analysis; Score system
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-13391-8

Type 2 diabetes (T2D) poses a significant global health burden. We developed a polygenic risk score (PRS) model based on genome-wide association study (GWAS) findings and integrated it with clinical data to predict T2D risk. This study analyzed electronic medical records from a major medical center in Taiwan, comprising 315,424 T2D cases and 141,484 controls. Fourteen genome-wide significant SNPs were identified and used to construct the T2D PRS. The integrated predictive model showed high accuracy (AUROC 0.842) and was validated in the Taiwan Biobank. A risk score ranging from 0 to 19 was established for clinical use. Phenome-wide association study (PheWAS) revealed links between PRSs and T2D-related complications, such as diabetic retinopathy and hypertension. Pathway analysis highlighted biological processes including IL-15 production and WNT/β-catenin signaling. Our findings support the use of PRSs in personalized T2D risk assessment and early prevention strategies.