A population-specific genomic reference panel for Taiwan: NHRI-RP-1.

BACKGROUND: To enhance the efficiency of identifying rare variants within the Taiwanese population and to support genome-wide association studies (GWAS) and imputation studies for genetic risk prediction in the Han population, we have developed the National Health Research Institutes (NHRI) reference panel (NHRI-RP-1). METHODS: NHRI-RP-1 is based on 2,561 whole genome sequences taken from the in-house NHRI datasets. Our objective was to optimize conditions of sample sizes (0.5K, 1K, 1.5K, 2K, 2.5K), minor allele frequency (MAF) thresholds (MAF ≥ 0.05, 0.01, 0.001, 2 × 10-4), and imputation quality (r2 ≥ 0, 0.3, 0.5) to build an aggregated genome reference panel for genetic medicine by comparing with worldwide references. Clinical applications and GWAS were then evaluated to demonstrate the capability of the reference panel. RESULTS: Among different combinations of relevant parameters, the NHRI-RP-1 (with a 2,500-sample size, MAF ≥ 2 × 10-4, r2 ≥ 0) demonstrated a superior F1 score on local match, genotype concordance and r-squared, as compared to those using worldwide reference genomes, particularly for rare MAFs. Furthermore, NHRI-RP-1 achieved over 95% accuracy for nine pathogenic variants present in the Taiwan Biobank and 93.49% and 92.9% accuracy for imputing two DRD1 variants. CONCLUSIONS: The use of different reference panels can influence the outcomes of GWAS. Our case studies demonstrate the utility of the NHRI-RP-1 for genetic medicine. Incorporating a population-specific panel such as NHRI-RP-1 can facilitate the development of prediction models using polygenic risk scores for diseases that are common in the Han population.