Complete genomic profiles of 1496 Taiwanese reveal curated medical insights.

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

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

Afiliação

Hsu JS; 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.
Wu DC; Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan.
Shih SH; Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan.
Liu JF; Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan.
Tsai YC; Department of Biomechatronics Engineering, National Taiwan University, Taipei 10617, Taiwan.
Lee TL; Department of Medical Genetics, National Taiwan University Hospital, Taipei 100226, Taiwan.
Chen WA; Department of Medical Genetics, National Taiwan University Hospital, Taipei 100226, Taiwan.
Tseng YH; Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 100025, Taiwan.
Lo YC; Department of Electrical Engineering, National Cheng-Kung University, Tainan 701401, Taiwan.
Lin HY; Department of Biomechatronics Engineering, National Taiwan University, Taipei 10617, Taiwan.
Chen YC; Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 100025, Taiwan.
Chen JY; Department of Electrical Engineering, National Cheng-Kung University, Tainan 701401, Taiwan.
Chou TH; Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 100025, Taiwan.
Chang DT; Department of Electrical Engineering, National Cheng-Kung University, Tainan 701401, Taiwan; Digital Technology Division, SinoPac Holdings, Taiwan.
Su MW; Institute of Biomedical Sciences, Academia Sinica, Taipei 115201, Taiwan.
Guo WH; Department of Biomechatronics Engineering, National Taiwan University, Taipei 10617, Taiwan.
Mao HH; Department of Biomechatronics Engineering, National Taiwan University, Taipei 10617, Taiwan.
Chen CY; 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.
Chen PL; 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

J Adv Res ; 2023 Dec 29.

Article em En | MEDLINE | ID: mdl-38159844

ABSTRACT

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.