On October 17, 2019, Prof. Chaolong Wang’s team from School of Public Health, Huazhong University of Science and Technology, published a paper, titled “Large-scale whole-genome sequencing of three diverse Asian populations in Singapore”, in Cell (IF=36.22). This study was led by Prof. Chaolong Wang, in collaboration with Prof. Jianjun Liu and the SG10K Consortium in Singapore. Prof. Chaolong Wang (lead contact of the paper) and Prof. Jianjun Liu are joint corresponding authors. Three members from Prof. Wang’s team, Drs. Degang Wu, Jinzhuang Dou and Ms. Xiaoran Chai are co-first authors. The paper was featured as the Cover Article by Cell.
Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. Due to its unique immigratory history, Singapore has diverse populations mostly comprised of Chinese, Malays and Indians, providing a snapshot of the genetic diversity across Asia. By whole-genome sequencing (WGS) 4810 Singaporeans, this study discovered 98.3 million SNPs and small insertions or deletions, more than half of which had not been catalogued in dbSNP, an authoritative database of genetic variants. Furthermore, 126 of the novel variants were annotated as “deleterious”, but reached >1% allele frequencies among Singaporeans, suggesting a potentially high risk of genetic misdiagnosis for Asian patients without an appropriate local reference database. This study, hence, provides critical information for advancing precision medicine in Asian populations.
Based on WGS data from both this study and the 1000 Genomes Project, the authors performed in-depth investigation of the population structure and evolutionary history of Asian populations. They confirmed that the three major ethnicities in Singapore capture majority of the genetic diversity across East, Southeast, and South Asia, and revealed a Malay-related novel ancestry component. Demographic inference further 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. In addition, the authors identified 20 candidate loci under natural selection, 13 of which were novel loci. Notably, 14 out of these 20 loci harbored robust association signals with complex traits or diseases, suggesting important contribution of natural selection to the phenotype diversity in humans.
Last but not least, the authors conducted extensive genotype imputation experiments. They showed that the WGS data reported by this study, in combination with those reported by the 1000 Genomes Project, can substantially improve imputation accuracy in diverse Asian and Oceanian populations, especially for rare variants. Given that imputation is an important technique widely used to increase the statistical power and resolution of genome-wide association studies, these results highlight the value of the data reported by this study to empower human genetics discovery across broad geographic regions.
For more details of the paper, please visit: https://doi.org/10.1016/j.cell.2019.09.019