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Cell. 2019 Oct 17;179(3):736-749.e15. doi: 10.1016/j.cell.2019.09.019.

Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore.

Author information

1
Computational and Systems Biology, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
2
Computational and Systems Biology, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore; Department of Bioinformatics and Computational Biology, Division of Quantitative Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
3
Computational and Systems Biology, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore.
4
Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore; Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4000, Australia.
5
Bioinformatics Core, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
6
Integrated Genome Analysis Platform (iGAP), Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
7
Computational and Systems Biology, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
8
Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
9
Department of Computer and Electrical Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL 33431, USA.
10
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
11
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore 117609, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
12
Department of Haematology, Singapore General Hospital, Singapore 169608, Singapore; National Cancer Centre Singapore, Singapore 169610, Singapore.
13
SingHealth Duke-NUS Institute of Precision Medicine, Singapore 169856, Singapore; Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore 169857, Singapore.
14
SingHealth Duke-NUS Institute of Precision Medicine, Singapore 169856, Singapore; Cancer and Stem Biology Program, Duke-NUS Medical School, Singapore 169857, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
15
Department of Surgery, National University Health System, Singapore 119228, Singapore.
16
Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828, Singapore.
17
Department of Neurology, National Neuroscience Institute, Singapore General Hospital Campus, Singapore 169608, Singapore; Neuroscience and Behavioural Disorders Program, Duke-NUS Medical School, Singapore 169857, Singapore.
18
Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore.
19
Personalised Medicine Service, Tan Tock Seng Hospital, Singapore 308433, Singapore.
20
Clinical Research and Innovation Office, Tan Tock Seng Hospital, Singapore 308433, Singapore.
21
Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore; Cardiovascular Research Institute, National University Heart Centre, Singapore 119074, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
22
Department of Cardiology, National Heart Centre Singapore, Singapore 169609, Singapore; Cardiovascular Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore; Cardiovascular Research Institute, National University Heart Centre, Singapore 119074, Singapore; Department of Cardiology, University Medical Center Groningen, Groningen 9713GZ, the Netherlands; The George Institute for Global Health, Newtown, NSW 2042, Australia.
23
Cardiovascular Research Institute, National University Heart Centre, Singapore 119074, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Christchurch Heart Institute, University of Otago, Christchurch 8011, New Zealand.
24
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore 169857, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
25
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Stem Cell and Regenerative Biology, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672; Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
26
Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. Electronic address: liuj3@gis.a-star.edu.sg.
27
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Computational and Systems Biology, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore. Electronic address: chaolong@hust.edu.cn.

Abstract

Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions or deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ∼24,800 years ago and experienced significant admixture with East Asians ∼1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, 14 of which harbored robust associations with complex traits and diseases. Finally, we show that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions.

KEYWORDS:

Asian populations; GWAS; admixture; demographic history; genetic diversity; imputation; natural selection; population structure; precision medicine; whole-genome sequencing

PMID:
31626772
DOI:
10.1016/j.cell.2019.09.019

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