Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore
2019
Wu, Degang | Dou, Jinzhuang | Chai, Xiaoran | Bellis, Claire | Wilm, Andreas | Shih, Chih Chuan | Soon, Wendy Wei Jia | Bertin, Nicolas | Lin, Clarabelle Bitong | Khor, Chiea Chuen | DeGiorgio, Michael | Cheng, Shanshan | Bao, Li | Karnani, Neerja | Hwang, William Ying Khee | Davila, Sonia | Tan, Patrick | Shabbir, Asim | Moh, Angela | Tan, Eng-King | Foo, Jia Nee | Goh, Liuh Ling | Leong, Khai Pang | Foo, Roger S.Y. | Lam, Carolyn Su Ping | Richards, Arthur Mark | Cheng, Ching-Yu | Aung, Tin | Wong, Tien Yin | Ng, Huck Hui | Liu, Jianjun | Wang, Chaolong | Ackers-Johnson, Matthew Andrew | Aliwarga, Edita | Ban, Kenneth Hon Kim | Bertrand, Denis | Chambers, John C. | Chan, Dana Leng Hui | Chan, Cheryl Xue Li | Chee, Miao Li | Chee, Miao Ling | Chen, Pauline | Chen, Yunxin | Chew, Elaine Guo Yan | Chew, Wen Jie | Chiam, Lynn Hui Yun | Chong, Jenny Pek Ching | Chua, Ivan | Cook, Stuart A. | Dai, Wei | Dorajoo, Rajkumar | Foo, Chuan-Sheng | Goh, Rick Siow Mong | Hillmer, Axel M. | Irwan, Ishak D. | Jaufeerally, Fazlur | Jāved, Āṣif | Jeyakani, Justin | Koh, John Tat Hung | Koh, Jia Yu | Krishnaswamy, Pavitra | Kuan, Jyn Ling | Kumari, Neelam | Lee, Ai Shan | Lee, Seow Eng | Lee, Sheldon | Lee, Yen-Ling | Leong, See Ting | Li, Zheng | Li, Peter Yiqing | Liew, Jun Xian | Liew, Oi Wah | Lim, Su Chi | Lim, Weng Khong | Lim, Chia Wei | Lim, Tingsen Benson | Lim, Choon Kiat | Loh, Seet Yoong | Lok, Au Wing | Chin, Calvin W.L. | Majithia, Shivani | Maurer-Stroh, Sebastian | Meah, Wee Yang | Mok, Shi Qi | Nargarajan, Niranjan | Ng, Pauline | Ng, Sarah B. | Ng, Zhenyuan | Ng, Jessica Yan Xia | Ng, Ebonne | Ng, Shi Ling | Nusinovici, Simon | Ong, Chin Thing | Pan, Bangfen | Pedergnana, Vincent | Poh, Stanley | Prabhakar, Shyam | Prakash, Kumar M. | Quek, Ivy | Sabanayagam, Charumathi | See, Wei Qiang | Sia, Yee Yen | Sim, Xueling | Sim, Wey Cheng | So, Jimmy | Soon, Dinna K.N. | Tai, E Shyong | Tan, Nicholas Y. | Tan, Louis C.S. | Tan, Hong Chang | Tan, Wilson Lek Wen | Tandiono, Moses | Tay, Amanda | Thakur, Sahil | Tham, Yih Chung | Tiang, Zenia | Toh, Grace Li-Xian | Tsai, Pi Kuang | Veeravalli, Lavanya | Verma, Chandra S. | Wang, Ling | Wang, Min Rui | Wong, Wing-Cheong | Xie, Zhicheng | Yeo, Khung Keong | Zhang, Liang | Zhai, Weiwei | Zhao, Yi
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.
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