Academic Journal
Rare variants discovery by extensive whole-genome sequencing of the Han Chinese population in Taiwan: Applications to cardiovascular medicine
| Title: | Rare variants discovery by extensive whole-genome sequencing of the Han Chinese population in Taiwan: Applications to cardiovascular medicine |
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| Authors: | Jyh-Ming Jimmy Juang, Tzu-Pin Lu, Ming-Wei Su, Chien-Wei Lin, Jenn-Hwai Yang, Hou-Wei Chu, Chien-Hsiun Chen, Yi-Wen Hsiao, Chien-Yueh Lee, Li-Mei Chiang, Qi-You Yu, Chuhsing Kate Hsiao, Ching-Yu Julius Chen, Pei-Ei Wu, Chien-Hua Pai, Eric Y. Chuang, Chen-Yang Shen |
| Source: | Journal of Advanced Research, Vol 30, Iss , Pp 147-158 (2021) |
| Publisher Information: | Elsevier, 2021. |
| Publication Year: | 2021 |
| Collection: | LCC:Medicine (General) LCC:Science (General) |
| Subject Terms: | Taiwan Biobank, Extensive whole-genome sequencing, De novo mutations, Cardiovascular diseases, Medicine (General), R5-920, Science (General), Q1-390 |
| More Details: | Introduction: A population-specific genomic reference is important for research and clinical practice, yet it remains unavailable for Han Chinese (HC) in Taiwan. Objectives: We report the first whole genome sequencing (WGS) database of HC (1000 Taiwanese genome (1KTW-WGS)) and demonstrate several applications to cardiovascular medicine. Methods: Whole genomes of 997 HC were sequenced to at least 30X depth. A total of 20,117 relatively healthy HC individuals were genotyped using a customized Axiom GWAS array. We performed a genome-wide genotype imputation technique using IMPUTE2. Results: We identified 26.7 million single-nucleotide variants (SNVs) and 4.2 million insertions-deletions. Of the SNVs, 16.1% were novel relative to dbSNP (build 152), and 34.2% were novel relative to gnomAD. A total of 18,450 healthy HC individuals were genotyped using a customized Genome-Wide Association Study (GWAS) array. We identified hypertension-associated variants and developed a hypertension prediction model based on the correlation between the WGS data and GWAS data (combined clinical and genetic models, AUC 0.887), and also identified 3 novel hyperlipidemia-associated variants. Each individual carried an average of 16.42 (SD = 3.72) disease-causing variants. Additionally, we established an online SCN5A (an important cardiac gene) database that can be used to explore racial differences. Finally, pharmacogenetics studies identified HC population-specific SNVs in genes (CYP2C9 and VKORC1) involved in drug metabolism and blood clotting. Conclusion: This research demonstrates the benefits of constructing a population-specific genomic reference database for precision medicine. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2090-1232 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2090123220302538; https://doaj.org/toc/2090-1232 |
| DOI: | 10.1016/j.jare.2020.12.003 |
| Access URL: | https://doaj.org/article/9022988ea22547ef96ec142bdbfe0cc8 |
| Accession Number: | edsdoj.9022988ea22547ef96ec142bdbfe0cc8 |
| Database: | Directory of Open Access Journals |
| ISSN: | 20901232 |
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| DOI: | 10.1016/j.jare.2020.12.003 |
| Published in: | Journal of Advanced Research |
| Language: | English |