1. Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore
- Author
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Degang Wu, Jinzhuang Dou, Xiaoran Chai, Claire Bellis, Andreas Wilm, Chih Chuan Shih, Wendy Wei Jia Soon, Nicolas Bertin, Clarabelle Bitong Lin, Chiea Chuen Khor, Michael DeGiorgio, Shanshan Cheng, Li Bao, Neerja Karnani, William Ying Khee Hwang, Sonia Davila, Patrick Tan, Asim Shabbir, Angela Moh, Eng-King Tan, Jia Nee Foo, Liuh Ling Goh, Khai Pang Leong, Roger S.Y. Foo, Carolyn Su Ping Lam, Arthur Mark Richards, Ching-Yu Cheng, Tin Aung, Tien Yin Wong, Huck Hui Ng, Jianjun Liu, Chaolong Wang, Matthew Andrew Ackers-Johnson, Edita Aliwarga, Kenneth Hon Kim Ban, Denis Bertrand, John C. Chambers, Dana Leng Hui Chan, Cheryl Xue Li Chan, Miao Li Chee, Miao Ling Chee, Pauline Chen, Yunxin Chen, Elaine Guo Yan Chew, Wen Jie Chew, Lynn Hui Yun Chiam, Jenny Pek Ching Chong, Ivan Chua, Stuart A. Cook, Wei Dai, Rajkumar Dorajoo, Chuan-Sheng Foo, Rick Siow Mong Goh, Axel M. Hillmer, Ishak D. Irwan, Fazlur Jaufeerally, Asif Javed, Justin Jeyakani, John Tat Hung Koh, Jia Yu Koh, Pavitra Krishnaswamy, Jyn Ling Kuan, Neelam Kumari, Ai Shan Lee, Seow Eng Lee, Sheldon Lee, Yen Ling Lee, See Ting Leong, Zheng Li, Peter Yiqing Li, Jun Xian Liew, Oi Wah Liew, Su Chi Lim, Weng Khong Lim, Chia Wei Lim, Tingsen Benson Lim, Choon Kiat Lim, Seet Yoong Loh, Au Wing Lok, Calvin W.L. Chin, Shivani Majithia, Sebastian Maurer-Stroh, Wee Yang Meah, Shi Qi Mok, Niranjan Nargarajan, Pauline Ng, Sarah B. Ng, Zhenyuan Ng, Jessica Yan Xia Ng, Ebonne Ng, Shi Ling Ng, Simon Nusinovici, Chin Thing Ong, Bangfen Pan, Vincent Pedergnana, Stanley Poh, Shyam Prabhakar, Kumar M. Prakash, Ivy Quek, Charumathi Sabanayagam, Wei Qiang See, Yee Yen Sia, Xueling Sim, Wey Cheng Sim, Jimmy So, Dinna K.N. Soon, E. Shyong Tai, Nicholas Y. Tan, Louis C.S. Tan, Hong Chang Tan, Wilson Lek Wen Tan, Moses Tandiono, Amanda Tay, Sahil Thakur, Yih Chung Tham, Zenia Tiang, Grace Li-Xian Toh, Pi Kuang Tsai, Lavanya Veeravalli, Chandra S. Verma, Ling Wang, Min Rui Wang, Wing-Cheong Wong, Zhicheng Xie, Khung Keong Yeo, Liang Zhang, Weiwei Zhai, Yi Zhao, Cardiovascular Centre (CVC), Lee Kong Chian School of Medicine (LKCMedicine), and School of Biological Sciences
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Male ,medicine.medical_specialty ,Demographic history ,Population ,Genome-wide association study ,HAPLOTYPE ,Biology ,VARIANTS ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,ANCESTRY ESTIMATION ,03 medical and health sciences ,0302 clinical medicine ,Whole-genome Sequencing ,Asian People ,HISTORY ,medicine ,Humans ,WIDE ASSOCIATION ,Medicine [Science] ,Selection, Genetic ,education ,ADAPTATION ,030304 developmental biology ,Whole genome sequencing ,Singapore ,0303 health sciences ,Genetic diversity ,education.field_of_study ,Whole Genome Sequencing ,Asian Populations ,Genome, Human ,Malaysia ,Human genetics ,GENOTYPE ,MODEL ,Genetics, Population ,Evolutionary biology ,Medical genetics ,Female ,HEALTH ,HUMAN-EVOLUTION ,030217 neurology & neurosurgery ,Imputation (genetics) - 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. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) National Research Foundation (NRF) Accepted version We acknowledge H.M. Kang, S. Das, A. Tan, F. Zhang, J. Terhorst, P.-R. Loh, and G. Hellenthal for helpful discussions and support from all participants and clinical research coordinators of the contributing cohorts and studies: the TTSH Healthy Control Workgroup, the SEED cohort, the Asian Sudden Cardiac Death in Heart Failure Study, the Singapore Heart Failure Outcomes and Phenotypes (SHOP) cohort, the Asian neTwork for Translational Research and Cardiovascular Trials (ATTRaCT), the Parkinson’s Disease Study, the Peranakan Genome Study, the Platinum Asian Genomes Project, the Bariatric Surgery Study, the National Heart Centre Singapore Biobank and SingHEART cohorts, and the GUSTO and S-PRESTO study groups. This study was supported by Singapore’s A*STAR (core funding and IAF-PP H17/01/a0/007), BMRC (SPF2014/001, SPF2013/002, SPF2014/003, SPF2014/004, and SPF2014/005), NMRC (CIRG/1371/2013, CIRG/1417/2015, CIRG/1488/ 2018, CSA-SI/0012/2017, CG/017/2013, CG/M006/2017_NHCS, TCR/013- NNI/2014, STaR/0011/2012, STaR2013/001, STaR/014/2013, STaR/0026/ 2015, TCR/006-NUHS/2013, TCR/012-NUHS/2014, TCR/004-NUS/2008, TCR/012-NUHS/2014, and center grants 2010-13 and 2013-2017), NRF (NRFF2016-03), National University of Singapore, SingHealth and DukeNUS, and Alexandra Health small innovative grant SIGII/15203 and funding from Huazhong University of Science and Technology, the Tanoto Foundation, the Lee Foundation, the Boston Scientific Investigator Sponsored Research Program and Bayer, the NSF (DEB-1753489), and the Alfred P. Sloan Foundation. The computation was partially performed on resources of the National Supercomputing Centre, Singapore (https://www.nscc.sg).
- Published
- 2019