Large-scale whole-genome sequencing of three diverse Asian populations in Singapore

Abstract

Asian populations are currently underrepresented in human genetics research. Here we present whole-genome sequencing data of 4,810 Singaporeans from three diverse ethnic groups: 2,780 Chinese, 903 Malays, and 1,127 Indians. Despite a medium depth of 13.7×, we achieved essentially perfect (>99.8%) sensitivity and accuracy for detecting common variants and good sensitivity (>89%) for detecting extremely rare variants with <0.1% allele frequency. We found 89.2 million single-nucleotide polymorphisms (SNPs) and 9.1 million small insertions and deletions (INDELs), more than half of which have not been cataloged in dbSNP. In particular, we found 126 common deleterious mutations (MAF>0.01) that were absent in the existing public databases, highlighting the importance of local population reference for genetic diagnosis. We describe fine-scale genetic structure of Singapore populations and their relationship to worldwide populations from the 1000 Genomes Project. In addition to revealing noticeable amounts of admixture among three Singapore populations and a Malay-related novel ancestry component that has not been captured by the 1000 Genomes Project, our analysis also identified some fine-scale features of genetic structure consistent with two waves of prehistoric migration from south China to Southeast Asia. Finally, we demonstrate that our data can substantially improve genotype imputation not only for Singapore populations, but also for populations across Asia and Oceania. These results highlight the genetic diversity in Singapore and the potential impacts of our data as a resource to empower human genetics discovery in a broad geographic region.

The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals

“…10 Recently, two studies reported population genomic dataset from Chinese non-invasive prenatal testing and Singapore Chinese population. 11 , 12 However, the low-depth sequencing data in these datasets limit the quantity of high-quality variants and accuracy of individual variants, especially rare variants. Considering the huge differences of genetic background and population characteristics between East Asians and Europeans, 13 and the lack of high-depth Chinese cohort genomic study, representative database from Chinese cohorts is a critical part for the missing diversity.…”

“Who is watching the watchdog?”: ethical perspectives of sharing health-related data for precision medicine in Singapore

“…Only Singaporean citizens or permanent residents over the age of 21 years were eligible to participate. This restriction was to re ect the recruitment parameters for precision medicine initiatives such as SG10K 12 in Singapore. Participants gave their written informed consent and received a supermarket voucher of SGD 50.00 for participation.…”

“…10 11 Singapore has invested signi cantly in developing PM with the large-scale whole-genome sequencing of Singapore's multi-ethnic Asian population (SG10k). 12 Some of this data has been linked to patients' electronic medical records (EMR) and used to support clinical care under the SingHealth Duke-NUS Institute of PRecISion Medicine (PRISM) initiative. 13 Singapore has the capacity to upscale this initiative across the public healthcare system, which is served by a national IT provider that can integrate health information from multiple sources, including EMR, biobanks and administrative databases.…”

"Who is Watching the Watchdog?": Ethical Perspectives of Sharing Health-related Data for Precision Medicine in Singapore

“…10 11 Singapore has invested significantly in developing PM with the large-scale whole-genome sequencing of Singapore's multi-ethnic Asian population (SG10k). 12 Some of this data has been linked to patients' electronic medical records (EMR) and used to support clinical care under the SingHealth Duke-NUS Institute of PRecISion Medicine (PRISM) initiative. 13 Singapore has the capacity to upscale this initiative across the public healthcare system, which is served by a national IT provider that can integrate health information from multiple sources, including EMR, biobanks and administrative databases.…”