National Precision Medicine (NPM) programme

Building a National Precision Medicine (NPM) programme – SG10K_Health

Background
The SG10K_Health project is a multi-institutional initiative developing an ‘all-of-Singapore' coordinated approach to precision medicine (PM). PM is a fast emerging field that seeks to improve treatment and prevent disease by considering individual and population genetic variation in genes, environment and lifestyle patterns. Through PM, patients may receive more accurate diagnosis, customised treatments achieving maximal benefit while minimising side effects, and reduced health care costs by avoiding ineffective treatments. At present, the Asian population is severely under-represented in the public genotypic databases. The current lack of large-scale control databases of Asian-specific genetic variation linked to clinical phenotypes is a significant barrier to the conduct of PM in Asia, to avoid mis-diagnosis and overtreatment due to the mistaken identification of pathogenic variants. The Singaporean population consists of three major ethnic groups, Chinese, Malay, and Indian, which together represent over 80% of the genetic variation in Asia. The presence of these three major ethnic groups in a single country thus offers a unique opportunity for Singapore, despite its small size, to contribute to global efforts in PM, complementing other large-scale efforts such as All of US and Genomics England.

Objectives
The SG10K_Health project aims to empower biomedical and genetic studies of Singapore and Asian-centric diseases by: 1) building local infrastructure and deep capabilities to generate, analyse and store human genetic data at population scale, in a safe, secure and rapid manner, 2) generating a diverse and rich control dataset of Asian populations for genetic association study of diseases, and 3) developing advanced analytical tools for genetic variants interpretation to derive disease risk predictions and identify clinically actionable variants. Notably, statistical estimates indicate that a genomic data set of 10,000 individuals will be sufficient to capture essentially all common alleles (ie more than 1% allele frequency) in our Singapore population.

Partners
Our collaborative academic partners include representatives from four A*STAR Research Institutes (BII, I2R, IHPC and SICS), three local medical schools (SingHealth Duke-NUS, Lee Kong Chian School of Medicine - NTU and Saw Swee Hock School of Public Health - NUS), Singapore Eye Research Institute (SERI), Tan Tock Seng Hospital (TTSH) and the National Supercomputing Centre (NSCC).

Publications & Press Release
Cell Magazine

Early research, the “SG10K_Pilot” conducted by many scientists involved in NPM and focusing on whole genome sequencing (WGS) in the Singaporean population was published in the prestigious scientific journal Cell (2019), where our work was complimented by being awarded the cover art design for the October 17th issue of the journal https://doi.org/10.1016/j.cell.2019.09.019).

    Key highlights:
  • Discovery of 52 million novel variants by 13.7× WGS of 4,810 Singaporeans.
  • Insights into population structure and evolutionary history of Asians.
  • Identification of 20 loci under selection that are enriched for GWAS (Genome-wide Association Studies) signals.
  • Substantial improvement of imputation in diverse Asian and Oceanian populations).

Professor Patrick Tan, Executive Director at GIS, Director at SingHealth Duke-NUS Institute of Precision Medicine (PRISM), and Professor at Duke-NUS Medical School, said,

“The project provides a pilot genetic map of Asian populations that allows us to measure precisely the genetic contribution to disease, and combine it with other sources of data within a data-driven healthcare system. Potentially, this will provide insights to prevent disease before it occurs, diagnose disease earlier, and ensure that therapies are deployed in a way that maximises clinical benefits while minimising adverse effects. This will benefit both Singapore and the Asian population at large by providing more effective and efficient healthcare services.”

To review the entire press release, please use link, to view Prof Tan’s on CNA discussing the study, please follow this link to YouTube, while the Straits Times feature is available here.

Programme investigators
Corresponding PIs: Prof Patrick Tan (GIS) and Prof Tai E Shyong (NUHs)
Co-investigators: Prof John Chambers (LKCMedicine), Dr Neerja Karnani (SICS), Prof Liu Jian Jun (GIS), Dr Shyam Prabhakar (GIS), Dr Birgit Eisenhaber (BII), Dr Chandra Verma (BII), Dr Sebastian Maurer-Stroh (BII), Dr Rick Goh (IHPC), Dr Sonia Davila (Duke-NUS), Dr Pavitra Krishnaswamy (I2R), Dr Sim Xueling (NUS), Dr Marie Loh (LKCMedicine), Prof Cheng Ching-Yu (SERI) and Dr Leong Khai Pang (TTSH).