Complete genomic profiles of 1496 Taiwanese reveal curated medical insights

Jacob Shujui Hsu; Dung-Chi Wu; Shang-Hung Shih; Jen-Feng Liu; Ya-Chen Tsai; Tung-Lin Lee; Wei-An Chen; Yi-Hsuan Tseng; Yi-Chung Lo; Hong-Ye Lin; Yi-Chieh Chen; Jing-Yi Chen; Ting-Hsuan Chou; Darby Tien-Hao Chang; Ming Wei Su; Wei-Hong Guo; Hsin-Hsiang Mao; Chien-Yu Chen; Pei-Lung Chen

doi:10.1016/j.jare.2023.12.018

Complete genomic profiles of 1496 Taiwanese reveal curated medical insights

J Adv Res. 2023 Dec 29:S2090-1232(23)00405-8. doi: 10.1016/j.jare.2023.12.018. Online ahead of print.

Authors

Jacob Shujui Hsu¹, Dung-Chi Wu², Shang-Hung Shih², Jen-Feng Liu³, Ya-Chen Tsai⁴, Tung-Lin Lee⁵, Wei-An Chen⁵, Yi-Hsuan Tseng⁶, Yi-Chung Lo⁷, Hong-Ye Lin⁴, Yi-Chieh Chen⁶, Jing-Yi Chen⁷, Ting-Hsuan Chou⁶, Darby Tien-Hao Chang⁸, Ming Wei Su⁹, Wei-Hong Guo⁴, Hsin-Hsiang Mao⁴, Chien-Yu Chen¹⁰, Pei-Lung Chen¹¹

Affiliations

¹ Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 100025, Taiwan; Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan.
² Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan.
³ Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan.
⁴ Department of Biomechatronics Engineering, National Taiwan University, Taipei 10617, Taiwan.
⁵ Department of Medical Genetics, National Taiwan University Hospital, Taipei 100226, Taiwan.
⁶ Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 100025, Taiwan.
⁷ Department of Electrical Engineering, National Cheng-Kung University, Tainan 701401, Taiwan.
⁸ Department of Electrical Engineering, National Cheng-Kung University, Tainan 701401, Taiwan; Digital Technology Division, SinoPac Holdings, Taiwan.
⁹ Institute of Biomedical Sciences, Academia Sinica, Taipei 115201, Taiwan.
¹⁰ Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan; Department of Biomechatronics Engineering, National Taiwan University, Taipei 10617, Taiwan. Electronic address: chienyuchen@ntu.edu.tw.
¹¹ Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 100025, Taiwan; Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan; Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei 100226, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan. Electronic address: paylong@ntu.edu.tw.

PMID: 38159844
DOI: 10.1016/j.jare.2023.12.018

Abstract

Introduction: The population of Taiwan has a long history of ethno-cultural evolution. The Taiwanese population was isolated from other large populations such as the European, Han Chinese, and Japanese population. The Taiwan Biobank (TWB) project has built a nationwide database, particularly for personal whole-genome sequence (WGS) to facilitate basic and clinical collaboration nationally and internationally, making it one of the most valuable public datasets of the East Asian population.

Objectives: This study provides comprehensive medical genomic findings from TWB WGS data, for better characterization of disease susceptibility and the choice of ideal treatment regimens in Taiwanese population.

Methods: We reanalyzed 1496 WGS using a PrecisionFDA Truth challenge winner method Sentieon DNAscope. Single nucleotide variants (SNV) and small insertions/deletions (INDEL) were benchmarked. We also analyzed pharmacogenomic (PGx) drug-associated alleles, and copy number variants (CNV). Multiple practicing clinicians reviewed and curated the clinically significant variants. Variant annotations can be browsed at TaiwanGenomes (https://genomes.tw).

Results: We found that each participant had an average of 6,870.7 globally novel variants and 75.3% (831/1103) of the participants harbored at least one PharmGKB-selected high evidence level human leukocyte antigen (HLA) risk allele. 54 PharmGKB-reported high-level instances of evidence of Cytochrome P450 variant-drug pairs, with a population frequency of over 13.2%. We also identified 23 variants in the ACMG secondary finding V3 gene list from 25 participants, suggesting that 1.67% (25/1496) of the population is harboring at least one medical actionable variant. Our carrier status analyses suggest that one in 25 couples (3.94%) would risk having offspring with at least one pathogenic variant, which is in line with rates found in Japan and Singapore. For pathogenic CNV, we detected 6.88% and 2.02% carrier rates for alpha thalassemia and spinal muscular atrophy, respectively.

Conclusion: Our study highlights the overall medical insights of a complete Taiwanese genomic profile.

Keywords: ACMG secondary finding V3 gene list; Carrier rates; Population allele frequency; Taiwan Biobank; Whole genome sequence.