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A high-resolution HLA imputation system for the Taiwanese population: a study of the Taiwan Biobank

The Pharmacogenomics Journal volume 20, pages 695–704 (2020)Cite this article

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Abstract

An imputation algorithm for human leukocyte antigen (HLA) is helpful for exploring novel disease associations. However, population-specific HLA imputation references are essential for achieving high imputation accuracy. In this study, a subset of 1012 individuals from the Taiwan Biobank (TWB) who underwent both whole-genome SNP array and NGS-based HLA typing were used to establish Taiwanese HLA imputation references. The HIBAG package was used to generate the imputation references for eight HLA loci at a two- and three-field resolution. Internal validation was carried out to evaluate the call threshold and accuracy for each HLA gene. HLA class II genes found to be associated with rheumatoid arthritis (RA) were validated in this study by the imputed HLA alleles. Our Taiwanese population-specific references achieved average HLA imputation accuracies of 98.11% for two-field and 98.08% for three-field resolution. The frequency distribution of imputed HLA alleles among 23,972 TWB subjects were comparable with PCR-based HLA alleles in general Taiwanese reported in the allele frequency net database. We replicated four common HLA alleles (HLA-DRB1*03:01, DRB1*04:05, DQA1*03:03, and DQB1*04:01) significantly associated with RA. The population-specific references provide an informative tool to investigate the associations of HLA variants and human diseases in large-scale population-based studies.

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Data availability

Supplementary information is available at The Pharmacogenomics Journal’s website. The codes performed for this work followed the instructions of the HIBAG author’s GitHub repository, https://github.com/zhengxwen/HIBAG/blob/master/vignettes/HIBAG.Rmd. The Taiwanese population-specific classifiers would be available from the authors upon request.

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Acknowledgements

This study was supported by research grants from the Ministry of Science and Technology, Taipei, Taiwan (MOST 105–2628-B010–003-MY4 and MOST 107–2314-B0101–004-MY2); Academia Sinica, Taipei, Taiwan; the Japan Agency for Medical Research and Development (AMED) under grant number JP18km0405205h0003 to S-SK and KT. No funding bodies had any role in the study design, data collection and analysis, publication decision, or paper preparation.

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  1. These authors contributed equally: Yu-Han Huang and Seik-Soon Khor

Authors and Affiliations

  1. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

    Yu-Han Huang, Yu-Ju Lin, Shu-Fen Liao & Mei-Hsuan Lee

  2. Department of Human Genetics, Graduate School of Medicine, the University of Tokyo, Toyo, Japan

    Seik-Soon Khor & Katsushi Tokunaga

  3. Department of Biostatistics, University of Washington, Seattle, WA, USA

    Xiuwen Zheng

  4. Institute of Statistical Science, Academia Sinica, Taipei, Taiwan

    Hsuan-Yu Chen, Ya-Hsuan Chang & Shu-Fen Liao

  5. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    Hou-Wei Chu, Pei-Ei Wu & Chen-Yang Shen

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Correspondence to Katsushi Tokunaga or Mei-Hsuan Lee.

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Huang, YH., Khor, SS., Zheng, X. et al. A high-resolution HLA imputation system for the Taiwanese population: a study of the Taiwan Biobank. Pharmacogenomics J 20, 695–704 (2020). https://doi.org/10.1038/s41397-020-0156-3

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