Actionable pharmacogenetic variants in Hong Kong Chinese exome sequencing data and projected prescription impact in the Hong Kong population

PLoS Genet. 2021 Feb 18;17(2):e1009323. doi: 10.1371/journal.pgen.1009323. eCollection 2021 Feb.

Abstract

Preemptive pharmacogenetic testing has the potential to improve drug dosing by providing point-of-care patient genotype information. Nonetheless, its implementation in the Chinese population is limited by the lack of population-wide data. In this study, secondary analysis of exome sequencing data was conducted to study pharmacogenomics in 1116 Hong Kong Chinese. We aimed to identify the spectrum of actionable pharmacogenetic variants and rare, predicted deleterious variants that are potentially actionable in Hong Kong Chinese, and to estimate the proportion of dispensed drugs that may potentially benefit from genotype-guided prescription. The projected preemptive pharmacogenetic testing prescription impact was evaluated based on the patient prescription data of the public healthcare system in 2019, serving 7.5 million people. Twenty-nine actionable pharmacogenetic variants/ alleles were identified in our cohort. Nearly all (99.6%) subjects carried at least one actionable pharmacogenetic variant, whereas 93.5% of subjects harbored at least one rare deleterious pharmacogenetic variant. Based on the prescription data in 2019, 13.4% of the Hong Kong population was prescribed with drugs with pharmacogenetic clinical practice guideline recommendations. The total expenditure on actionable drugs was 33,520,000 USD, and it was estimated that 8,219,000 USD (24.5%) worth of drugs were prescribed to patients with an implicated actionable phenotype. Secondary use of exome sequencing data for pharmacogenetic analysis is feasible, and preemptive pharmacogenetic testing has the potential to support prescription decisions in the Hong Kong Chinese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asian People / genetics
  • Cohort Studies
  • Exome Sequencing / methods*
  • Gene Frequency
  • Genotype
  • Hong Kong
  • Humans
  • Pharmacogenetics / methods*
  • Pharmacogenetics / statistics & numerical data
  • Pharmacogenomic Testing / methods
  • Pharmacogenomic Testing / statistics & numerical data
  • Pharmacogenomic Variants / genetics*
  • Phenotype
  • Prescriptions / statistics & numerical data*
  • Reproducibility of Results

Grants and funding

This study was supported by the Society for the Relief of Disabled Children (BHYC), the Health and Medical Research Fund (BHYC), Li Ka Shing Donation Account: Enhanced New Staff Start-up Packages (PHYC), the Children's Heart Foundation (BHYC), and the Edward and Yolanda Wong Fund (BHYC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.