2025/12/30 by W. F. Liao, Chun-Wen Cheng, Ya-Wen Chang +5 · 1 voice
Biochemistry, Genetics and Molecular Biology · Psychology · #Genetic Associations and Epidemiology #BRCA gene mutations in cancer #Cognitive Abilities and Testing
paper · doi:10.2337/db25-0357
openalex created_date 2025/12/30 · openalex publication_date 2025/12/30 · openalex updated_date 2026/08/01
Type 2 diabetes is a complex disease influenced by both genetic and environmental factors. Although polygenic risk scores (PRS) and family history (FH) are established predictors, their combined utility in East Asian populations remains unclear. In this study, we analyzed 111,899 unrelated participants from the Taiwan Biobank with linkage to nationwide health registry data. We constructed transancestry, East Asian-specific, and European-derived PRS and assessed their associations with type 2 diabetes. The transancestry PRS improved the explained variance in disease risk compared with ancestry-specific PRS and FH. FH, particularly sibling history, also showed a strong association with type 2 diabetes. When combined, PRS and FH contributed independently and additively, improving predictive performance. These findings demonstrate that PRS and FH are independent yet complementary risk indicators and support the application of transancestry PRS models in East Asian populations. Incorporating both genetic and familial risk factors may enhance early detection and facilitate more personalized prevention strategies for type 2 diabetes. ARTICLE HIGHLIGHTS: Type 2 diabetes is influenced by genetic and environmental factors. Although polygenic risk scores (PRS) and family history (FH) are established predictors, their combined utility in East Asian populations is unclear. We evaluated the predictive performance of PRS and the independent and joint effects of PRS and FH on diabetes risk in an East Asian population. The transancestry PRS explained more variance than ancestry-specific PRS and FH. PRS and FH were independently predictive, and their combination improved prediction, with stronger effects in men. Sibling history showed the strongest familial association. Integrating PRS and FH may enhance diabetes risk prediction in East Asian populations.