Taiwan’s Genetic Blueprint: The HLA Region’s Role in Health and Drug Safety

Summary

A research team from Taipei Medical University (TMU) led by Prof. Wei Chiao Chang, has developed a highly precise HLA imputation reference panel tailored to the Taiwanese Han Chinese population. This study provides the most comprehensive genetic dataset of HLA variations in this population, uncovering novel associations with diseases and adverse drug reactions. By enhancing the accuracy of genetic analysis, this research lays the foundation for safer, population-specific precision medicine, advancing personalized healthcare.

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The Novelty (What)  

This study successfully developed a population-specific human leukocyte antigen (HLA) imputation reference panel tailored to the Taiwan Han Chinese population, enabling precise genetic and phenotypic profiling of the HLA region. Using a cohort-based model that combined high-resolution HLA sequencing and genotype data from 845 individuals, the researchers applied the panel to analyze data from 59,448 participants, achieving high accuracy in predicting HLA alleles. Key findings include the identification of 15 novel HLA-phenotype associations, such as the link between HLA-B position 138 and ankylosing spondylitis, as well as the prevalence of ADR-related alleles like HLA-B*58:01. This research sets the stage for future studies to explore the role of HLA variations in broader disease phenotypes and supports the advancement of pharmacogenomic applications in precision medicine.

The Background (Why)

The human leukocyte antigen (HLA) region on chromosome 6 is a highly diverse cluster of genes critical to immune system function, enabling the body to distinguish self from non-self through antigen presentation. This genetic diversity is associated with susceptibility to various diseases, such as rheumatoid arthritis and ankylosing spondylitis, as well as severe adverse drug reactions (ADRs). However, past studies have primarily focused on populations in Europe, Japan, and Korea, leaving the unique genetic and phenotypic characteristics of the Taiwan Han Chinese population underexplored. Moreover, while accurate, sequencing-based methods are costly, labor-intensive, and impractical for extensive cohort studies. To address these limitations, this study developed an imputation reference panel using advanced genotype data from the Taiwan Biobank, incorporating the expanded TWBv2 SNP array. This approach enables large-scale investigations of HLA variations and their clinical significance, providing a vital tool for bridging gaps in understanding population-specific genetic diversity.

 

The SDG impact (Big Why)

Adverse drug reactions (ADRs) are a significant global health concern, contributing to 10% of hospital admissions in developed countries and causing substantial morbidity and mortality, according to the World Health Organization (WHO). Addressing this issue is critical to improving drug safety and reducing healthcare burdens worldwide. This research supports SDG 3 (Good Health and Well-being) by advancing pharmacogenomic insights through the identification of ADR-related HLA alleles prevalent in the Taiwanese population, such as HLA-B*58:01, which is linked to severe drug reactions like allopurinol hypersensitivity. Additionally, the study aligns with SDG 9 (Industry, Innovation, and Infrastructure) by fostering innovative genomic research and creating tools like the population-specific HLA imputation reference panel, which enhances healthcare infrastructure for precision medicine.

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Look for More Information

Original Article: Phenomic landscape and pharmacogenomic implications for HLA region in a Taiwan Han Chinese population