Precision medicine in Asia, for Asia

Asians have traditionally been underrepresented in population health studies. Researchers led by Prof John Chambers aim to change that with the SG100K project.

Beneath the white coats and stethoscopes, medicine is a numbers game. From blood pressure readings to the concentration of specific molecules in bodily fluids, measurements provide doctors with clues about an individual’s health—not just in the present, but also the future. High levels of cholesterol in the blood, for instance, can be used to assess one’s future risk of heart disease and stroke.

The algorithms and formulas for calculating disease susceptibility matter, but for decades, they have been shaped by studies performed almost exclusively on Western populations. Transplanting those formulas into Asian contexts is a useful starting point for managing chronic and noncommunicable diseases such as heart conditions and diabetes. However, important differences in genetics, environments and behaviours may cloud diagnoses and delay interventions in Asian patients.

Prof John Chambers, President’s Chair in Cardiovascular Epidemiology at NTU’s Lee Kong Chian School of Medicine (LKCMedicine), points out that the differences between Western and Asian populations are medically non-trivial. “For example, the typical Asian has a risk of diabetes that’s about three to four times higher than that of a European. While 10-20% of Europeans might develop diabetes at some point in their lives, that figure is 50-60% among Asians, so it’s a huge difference,” he says. Clearly, a one-size-fits-all approach to evaluating disease susceptibility is less than ideal.

Health from the inside out

Seeking to better calibrate how diseases are treated in Asian populations, Prof Chambers plans to create a comprehensive biomedical database consisting of 100,000 Singaporeans—what he calls the SG100K project.

With S$22 million (US$16.2 million) in research funding secured from the National Medical Research Council of Singapore, Prof Chambers and collaborators at the Duke-National University of Singapore Medical School, Saw Swee Hock School of Public Health, SingHealth and National University Hospital of Singapore, will conduct a thorough investigation of the physiology and biology of the SG100K study participants. Their methodology involves health surveys, cognition tests, medical imaging and the collection of a diverse range of samples from each person.

“There’s a lot we can see about somebody by looking at them, or recording from the surface of their bodies. But what we really want to get into is the way the cells and the tissues are behaving, so we also take blood, urine, saliva, skin tapes and even stool samples to apply state-of-the-art molecular analysis to,” he explains. Part of that analysis will be run at the Singapore Phenome Centre (SPC), an interdisciplinary research platform launched in 2015 and headed by Prof Wang Yulan of LKCMedicine.

Prof Wang’s expertise lies in metabolomics—the large-scale study of small molecules, or metabolites, found in biological samples. If the body were a factory, metabolites may be regarded as its outputs. By understanding the nature and quantity of these outputs—be they useful products or waste—one can glean insights into the efficiency of the system that generates them.

Using two powerful and complementary techniques—nuclear magnetic resonance and mass spectrometry—the SPC will generate comprehensive metabolic profiles from patient samples collected by Prof Chambers’ team. “Metabolic abnormalities typically precede the onset of disease symptoms, which means that metabolites can be used as early indicators of health problems on the horizon,” Prof Wang notes.

Prediction, precision, prevention

The deep molecular analysis done at SPC, combined with the survey and observational data collected by Prof Chambers’ team, will create a holistic database on an Asian cohort spanning multiple ethnicities.

“Almost no other international studies have this depth of phenotyping, so that will really set us apart in terms of being able to answer big questions about the differences between Asians and Europeans,” Prof Chambers says.

While the goal of recruiting 100,000 participants and profiling all of them so thoroughly may sound daunting, Prof Chambers believes that the cost and effort are worth it. “The SG100K project will give Singapore a seat at the table of international leaders of population health research,” he adds.

But more importantly, he notes, the dataset generated will help realise the ideal of precision medicine, where “the right patient gets the right treatment, at the right time and at the right dose, to maximise clinical effectiveness and sustain health”.

The SG100K project is therefore just the starting point for many future studies that will shape biomedical research and healthcare in the region as well as internationally. If all goes well, predictive algorithms tailor-made for assessing disease susceptibility in Asian populations will emerge and lead to improved patient outcomes as well as more efficient deployment of medical resources.

Prof Chambers emphasises that the long-term success of the SG100K project depends on multi-institutional cooperation—the coming together of hands and minds to build the cohort and to analyse and understand the enormous amount of rich data generated.

“It’s a privilege to be the chief investigator on this project,” he says. “But I could not achieve one percent of this by myself. This really is team science.”

The article appeared first in NTU’s research & innovation magazine Pushing Frontiers (issue #16, February 2020). 

You may also like...