SINGAPORE – Imagine an advanced genetic scorecard that can tell you how likely you are to develop common chronic conditions like diabetes or high blood pressure, based on genetic markers specific for Asians.

Genetic markers can help link an inherited disease with the gene responsible.

Tan Tock Seng Hospital’s (TTSH) Molecular Diagnostic Laboratory is now able to offer multi-gene testing to patients and to facilitate clinical research for the prediction and prevention of diseases.

One of the areas these capabilities will be applied is in predicting heart disease.

In a press briefing at TTSH on Tuesday, Adjunct Associate Professor Leong Khai Pang, head of the hospital’s personalised medicine service, said that the hospital has been offering single-gene pharmacogenetic tests since 2017. These are tests done to see how a patient responds to certain medications.

Common examples are tests for drugs like carbamazepine, which is used to treat certain types of seizures, and allopurinol, which is used to treat gout.

To expand the lab’s capabilities, the hospital collaborated with biotechnology company Thermo Fisher Scientific in 2022 to develop a customised array with Asian-specific markers. An array allows scientists to perform an experiment on thousands of genetic markers at the same time.

Through this partnership, TTSH is now able to simultaneously assess multiple genes, and implement polygenic risk scores, which is a measure of disease risk based on an individual’s genetic information.

Associate Professor Rinkoo Dalan, a senior consultant at TTSH’s department of endocrinology, said that the lab and clinicians will be working together on a three-year Predict-2-Prevent research trial from August 2023 to identify patients at risk of a heart attack.

About 1,000 patients who have diabetes, high blood pressure, high cholesterol or obesity will be recruited for this personalised cardiometabolic research management programme, which is sponsored by Ng Teng Fong Foundation and the National Healthcare Group.

Fifty thousand gene variants will be assessed to derive an individual’s polygenic risk score. The risk score is then interpreted in context of the trial’s participants, and the top 20 per cent is considered high risk.

“The problem with cardiovascular risk is that not one gene gives a risk – it’s a mixture of many genes combined together that confers a higher cardiovascular risk. So we actually need to look at all the risks and then combine it together as one single risk score,” said Prof Rinkoo.

These patients will then receive more intensive treatment or engaged more to make lifestyle changes.

“We also want to make the message clear that it is not genetic destiny. (Having a high risk) just means that you have to take extra care of yourself,” said Prof Rinkoo.

The trial will also study the cost involved in doing polygenic risk scoring for the entire Singapore population, and the cost-savings if cardiovascular risk is managed properly in the long run. To help clinicians communicate genetic risks better, qualitative studies will also be done on how patients perceive the risk in terms of management, added Prof Rinkoo.

She said the efficacy of using polygenic risk score to predict heart disease will also be assessed using surrogate measures of cardiovascular risk.

These measures include using ultrasound to assess the thickness of carotid arteries, the major blood vessels in the neck that provide the brain’s blood supply. The thicker the carotid arteries are, the more likely that a person has cardiovascular risk.

Dr Goh Liuh Ling, senior principal scientific officer at TTSH’s personalised medicine service, said such efforts to drive precision medicine are also aligned with the nation’s move towards preventative healthcare under Healthier SG.

“We envision a future in which the capability to stratify patients based on risks of developing a certain disease will allow individuals to exercise early intervention and ultimately lead to healthier lives and, in some cases, avoid hefty costs associated with managing disease.”

Dr Goh added: “This will not only deliver value to patients but also bring us one step closer toward realising Singapore’s goal of shifting from sick care to preventative healthcare, and offer a sustainable way to serve the evolving healthcare needs of Singaporeans.”