Journal
JOURNAL OF ADVANCED RESEARCH
Volume 30, Issue -, Pages 147-158Publisher
ELSEVIER
DOI: 10.1016/j.jare.2020.12.003
Keywords
Taiwan Biobank; Extensive whole-genome sequencing; De novo mutations; Cardiovascular diseases
Categories
Funding
- Ministry of Science and Technology, Taiwan [MOST 104-2314-B-002-193-MY3, MOST 106-2314-B-002-047-MY3, MOST 106-2314-B-002-134-MY2, MOST 106-2314-B-002-206, MOST 107-2314-B-002-009, MOST 108-2314-B-002-007, MOST 107-2314-B-002-261-MY3]
- Taiwan Health foundation
- National Taiwan University Hospital [NTUH 105-S3077, NTUH-105-S2995, NTUH-UN105-012, NTUH 106-S3469, NTUH 106-S3458, NTUH 106-018]
- National Taiwan University [GTZ300]
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This study established the first genomic database for Han Chinese in Taiwan, identifying hypertension and hyperlipidemia-associated variants and developing prediction models. Additionally, an online database for exploring racial differences in the important cardiac gene SCN5A was created, and population-specific SNVs in genes related to drug metabolism and blood clotting were discovered.
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. (C) 2020 The Authors. Published by Elsevier B.V.
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