Abstract / Summary
Background Non-communicable diseases (NCDs) impose substantial population burden. Their polygenic architecture informs early risk stratification through polygenic risk scores (PRS). Previous studies reported elevated-PRS burden comparable to some modifiable risk factors (MRFs), yet evidence remains confined to European populations. We quantified the PRS-attributable NCD burden in Taiwan. Methods Linking Taiwan Biobank and National Health Insurance Research Database (N = 140K), we analyzed 42 high-burden NCDs. Elevated genetic risk (PRSe; top 10%) was assessed using Cox models. We estimated population attributable fractions (PAFs) and disability-adjusted life years (DALYs) using Taiwan-specific estimates from Global Burden of Disease 2023, and examined associations between an integrated PRS (iPRS) and healthcare utilization. Findings Strongest PRSe associations occurred for atrial fibrillation (AFib; HR = 3.56 [95% CI: 3.23-3.92]) and gout (2.41 [2.33-2.49]), yielding PAFs of 20% and 12%, respectively, while population-level attributable DALYs were largest for type 2 diabetes (T2D), intracranial hemorrhage (ICH), and lung cancer. At the individual level, PRS_e corresponded to 1.50 [1.42-1.57] healthy life-years lost for T2D and 0.57 [0.40-0.76] for ICH, approaching 2.4 years for the top 1% PRS. Polygenic attributable burden was overall greater in men. For several diseases, PRS_e-associated PAF and DALYs exceeded those of individual MRFs (e.g., smoking, alcohol use). Top-decile iPRS was linked to 23.9% (15.0-33.6%) more hospital days, 19.1% (13.2-25.3%) more inpatient visits, and 9.6% (6.9-12.4%) more outpatient visits. Interpretation Polygenic risk accounts for a measurable--and for several diseases, MRF-comparable--share of NCD burden in Taiwan, providing a quantitative foundation for integrating genetic liability into preventive care and health planning.