PMID- 38159844 OWN - NLM STAT- Publisher LR - 20240107 IS - 2090-1224 (Electronic) IS - 2090-1224 (Linking) DP - 2023 Dec 29 TI - Complete genomic profiles of 1496 Taiwanese reveal curated medical insights. LID - S2090-1232(23)00405-8 [pii] LID - 10.1016/j.jare.2023.12.018 [doi] AB - 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. CI - Copyright (c) 2023. Production and hosting by Elsevier B.V. FAU - Hsu, Jacob Shujui AU - Hsu JS AD - 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. FAU - Wu, Dung-Chi AU - Wu DC AD - Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan. FAU - Shih, Shang-Hung AU - Shih SH AD - Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan. FAU - Liu, Jen-Feng AU - Liu JF AD - Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan. FAU - Tsai, Ya-Chen AU - Tsai YC AD - Department of Biomechatronics Engineering, National Taiwan University, Taipei 10617, Taiwan. FAU - Lee, Tung-Lin AU - Lee TL AD - Department of Medical Genetics, National Taiwan University Hospital, Taipei 100226, Taiwan. FAU - Chen, Wei-An AU - Chen WA AD - Department of Medical Genetics, National Taiwan University Hospital, Taipei 100226, Taiwan. FAU - Tseng, Yi-Hsuan AU - Tseng YH AD - Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 100025, Taiwan. FAU - Lo, Yi-Chung AU - Lo YC AD - Department of Electrical Engineering, National Cheng-Kung University, Tainan 701401, Taiwan. FAU - Lin, Hong-Ye AU - Lin HY AD - Department of Biomechatronics Engineering, National Taiwan University, Taipei 10617, Taiwan. FAU - Chen, Yi-Chieh AU - Chen YC AD - Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 100025, Taiwan. FAU - Chen, Jing-Yi AU - Chen JY AD - Department of Electrical Engineering, National Cheng-Kung University, Tainan 701401, Taiwan. FAU - Chou, Ting-Hsuan AU - Chou TH AD - Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 100025, Taiwan. FAU - Chang, Darby Tien-Hao AU - Chang DT AD - Department of Electrical Engineering, National Cheng-Kung University, Tainan 701401, Taiwan; Digital Technology Division, SinoPac Holdings, Taiwan. FAU - Su, Ming Wei AU - Su MW AD - Institute of Biomedical Sciences, Academia Sinica, Taipei 115201, Taiwan. FAU - Guo, Wei-Hong AU - Guo WH AD - Department of Biomechatronics Engineering, National Taiwan University, Taipei 10617, Taiwan. FAU - Mao, Hsin-Hsiang AU - Mao HH AD - Department of Biomechatronics Engineering, National Taiwan University, Taipei 10617, Taiwan. FAU - Chen, Chien-Yu AU - Chen CY AD - 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. FAU - Chen, Pei-Lung AU - Chen PL AD - 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. LA - eng PT - Journal Article DEP - 20231229 PL - Egypt TA - J Adv Res JT - Journal of advanced research JID - 101546952 SB - IM OTO - NOTNLM OT - ACMG secondary finding V3 gene list OT - Carrier rates OT - Population allele frequency OT - Taiwan Biobank OT - Whole genome sequence COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/01/02 11:45 MHDA- 2024/01/02 11:45 CRDT- 2023/12/30 19:17 PHST- 2023/08/14 00:00 [received] PHST- 2023/12/03 00:00 [revised] PHST- 2023/12/27 00:00 [accepted] PHST- 2024/01/02 11:45 [pubmed] PHST- 2024/01/02 11:45 [medline] PHST- 2023/12/30 19:17 [entrez] AID - S2090-1232(23)00405-8 [pii] AID - 10.1016/j.jare.2023.12.018 [doi] PST - aheadofprint SO - J Adv Res. 2023 Dec 29:S2090-1232(23)00405-8. doi: 10.1016/j.jare.2023.12.018.