Pharmacogenomic Calling From Whole-Exome Sequencing in the Taiwanese Population-A Real-World Experience

Pharmacogenomics (PGx) enables precision medicine by improving efficacy and reducing adverse drug reactions, but implementation is limited by testing burden and ethnic variability. With whole-exome sequencing (WES) increasingly applied in Taiwan, we evaluated its feasibility for PGx analysis.

We analyzed WES data from 3562 individuals at a tertiary medical center. PGx calling was performed on 17 pharmacogenomic loci using Aldy, and HLA typing was inferred using the high-quality dictionary (HLA-HD). Phenotypes were annotated using the Pharmacogenomics Clinical Annotation Tool (PharmCAT).

After comparison with WGS and sequencing-based HLA typing data, 14 pharmacogenomic loci were found to be suitable for PGx calling from WES. On average, each individual carried approximately 2.4 actionable phenotypes across 14 genes. Compared with East Asian and European populations, the Taiwanese population has a greater frequency of actionable pharmacogenomic phenotypes for G6PD deficiency (2%) and HLA-B*58:01 (21%). Additionally, the CYP2C19, CYP3A5, NUDT15, and HLA-B*15:02 actionable phenotypes occur at frequencies similar to those of East Asians but are more frequent than those in Europeans. Our WES findings are generally consistent with previous Taiwanese WGS and array data.

Ethnic differences in PGx variants underscore the need for population-specific data. The high prevalence of actionable phenotypes in Taiwanese individuals supports the use of WES, which effectively captures certain key pharmacogenes for routine PGx testing.