Population-Specific Polygenic Risk Scores Developed for the Han Chinese

Abstract

Predicting complex disease risks based on individual genomic profiles is an advancing field in human genetics1,2. However, most genetic studies have focused on European populations, creating a global imbalance in precision medicine and underscoring the need for genomic research in non-European groups3,4. The Taiwan Precision Medicine Initiative (TPMI) recruited over half a million Taiwanese residents, providing a large dataset of genetic profiles and electronic medical record data for the Han Chinese. Using extensive phenotypic data, we conducted comprehensive genomic analyses of Han Chinese across the medical phenome. These analyses identified population-specific genetic risk variants and novel findings for various complex traits. We developed polygenic risk scores, demonstrating strong predictive performance for conditions such as cardiometabolic diseases, autoimmune disorders, cancers, and infectious diseases. We observed consistent findings in an independent dataset, Taiwan Biobank, and among East Asians in the UK Biobank and the All of Us Project. The identified genetic risks accounted for up to 10.3% of the overall health variation in the TPMI cohort. Our approach of characterizing the phenome-wide genomic landscape, developing population-specific risk prediction models, assessing their performance, and identifying the genetic impact on health, serves as a model for similar studies in other diverse study populations.