E-Shyong Tai

• MB ChB, PhD
• Professor (Associate) at National University Health System

Precision medicine (PM) research in recent years has witnessed a remarkable surge in large-scale population genomics programs. In 2017, Singapore initiated the National Precision Medicine (NPM) program, a three-phase national strategy driving PM research, innovation, and enterprise capitalizing on Singapore’s unique multi-ancestral Asian population...

To identify biomarkers and pathways to Type-2 diabetes (T2D), a major global disease, we completed array-based epigenome-wide association in whole blood in 5,709 Asian people. We found 323 Sentinel CpGs (from 314 genetic loci) that predict future T2D. The CpGs reveal coherent, nuclear regulatory disturbances in canonical immune activation pathways,...

Background Gene-environment interactions may enhance our understanding of hypertension. Our previous study highlighted the importance of considering psychosocial factors in gene discovery for blood pressure (BP) but was limited in statistical power and population diversity. To address these challenges, we conducted a multi-population genome-wide as...

Context Type 2 diabetes (T2D) is a major global concern, with Asia at its epicenter in recent years. Proteins, products of gene transcription, serve as dynamic biomarkers for pinpointing perturbed pathways in disease development. Previous T2D proteomic association studies primarily focused on European populations. Objective The aim of this study w...

Background: RETFound, a self-supervised, retina-specific foundation model (FM), showed potential in downstream applications. However, its comparative performance with traditional deep learning (DL) models remains incompletely understood. This study aimed to evaluate RETFound against three ImageNet-pretrained supervised DL models (ResNet50, ViT-base...

Background Digital health (DH) technologies provide scalable and cost-effective solutions to improve population health but face challenges of uneven adoption and high attrition, particularly among vulnerable and minority groups. Purpose This study explores factors influencing DH adoption in a multicultural population and identifies strategies to i...

Aims/hypothesis This study aims to explore the association between plasma metabolites and chronic kidney disease progression in individuals with type 2 diabetes. Methods We performed a comprehensive metabolomic analysis in a prospective cohort study of 5144 multi-ancestral individuals with type 2 diabetes in Singapore, using eGFR slope as the prim...

The biomarkers connecting obesity and cardiometabolic diseases are not fully understood. We aimed to 1) evaluate the associations between BMI, waist circumference (WC), and ∼5,000 plasma proteins (SomaScan V4), 2) identify protein signatures of BMI and WC, and 3) evaluate the associations between the protein signatures and cardiometabolic health, i...

Aims Women with gestational diabetes (GDM) have increased lifetime risk of developing diabetes. We aim to determine the factors contributing to poor adherence of the postpartum oral glucose tolerance test (OGTT) and identify key predictors to postpartum dysglycaemia in our Asian cohort. Methods We conducted a retrospective cohort study of women wi...

Structural variants (SVs) are significant contributors to inter-individual genetic variation associated with traits and diseases. Current SV studies using whole-genome sequencing (WGS) have a largely Eurocentric composition, with little known about SV diversity in other ancestries, particularly from Asia. Here, we present a WGS catalogue of 73,035...

Purpose: Digital health interventions (DHIs) offer scalable and cost-effective solutions for preventive healthcare, yet their adoption remains uneven, particularly among vulnerable and minority groups. High attrition rates also challenge their long-term effectiveness. This study aims to explore the factors and behavioural mechanisms influencing DHI...

Background: Statins are a first line treatment for reducing cardiovascular risk. While drug-drug interactions which cause symptomatic side effects are well known, drug-drug interactions which decrease statin effectiveness are poorly understood. Methods: A multicentre prospective observational study of 1362 participants on chronic statin medication...

Background: Blended mobile health (mHealth) interventions – combining self-guided and human support components – could play a major role in preventing non-communicable diseases (NCDs) and common mental disorders (CMDs). This protocol paper describes a sequential, multiple assignment, randomised trial aimed at (i) evaluating the effectiveness and co...

Glycine is deficient in individuals with obesity but improves following bariatric surgery. Glycine deficiency could impair glutathione (GSH) synthesis and worsen oxidative stress. We examined the impact of obesity-associated glycine deficiency and bariatric surgery on GSH synthesis. Twenty-one participants with severe obesity and twenty-one healthy...

Type 2 diabetes (T2D) is a major global concern, with Asia at its epicenter in recent years. Proteins, products of gene transcription, serve as dynamic biomarkers for pinpointing perturbed pathways in disease development. To understand the protein function in incident T2D, we examined the association of 4,775 plasma proteins with incident T2D in a...

Background The E val U ation of goal-di R ected activities to pr O mote well-be I ng and he A lth (EUROIA) scale is a novel patient-reported measure that was administered to individuals with chronic heart failure (CHF). It assesses goal-directed activities that are self-reported as being personally meaningful and commonly utilized to optimize healt...

Hereditary Cancer makes up around 5–10% of all cancers. It is important to diagnose hereditary cancer in a timely fashion, as not only do patients require long-term care from a young age, but their relatives also require management. The main approach to capture at-risk relatives is cascade testing. It involves genetic testing of relatives of the fi...

Statins are a first line treatment for reducing cardiovascular risk, however the individual clinical benefit of statins remains highly variable. To understand the clinical impact of individual statin metabolites on long-term clinical outcomes, we conducted a 5-year, multicentre, prospective, observational trial of 1362 cardiology patients across tw...

Background Glycine is an integral component of the human detoxification system as it reacts with potentially toxic exogenous and endogenously produced compounds and metabolites via the glycine conjugation pathway for urinary excretion. Because individuals with obesity have reduced glycine availability, this detoxification pathway may be compromised...

Background Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine‐needle aspiration (FNA) biopsies of cytologically indeterminat...

Background Individual appraisals of personal well-being consider a spectrum of constructs including the reflections on the degree to which one’s life is ultimately secure, meaningful, or valued in the context of dynamic changes in their bio-psycho-social environments. Standardized questionnaires for well-being evaluate an ideal state of health whic...

BACKGROUND The Dietary Approaches to Stop Hypertension (DASH) diet score lowers blood pressure (BP). We examined interactions between genotype and the DASH diet score in relation to systolic BP. METHODS We analyzed up to 9 420 585 single nucleotide polymorphisms in up to 127 282 individuals of 6 population groups (91% of European population) from...

Growth mindsets and self-efficacy beliefs have been known to predict and promote resilience, challenge seeking, and improved outcomes in areas such as education and intelligence. However, little is known about the role of these two potentially influential beliefs in the context of type 2 diabetes (T2D), specifically in terms of whether and in which...

Objective We examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP). Methods We analyzed up to 9,420,585 biallelic imputed single nucleotide polymorphisms (SNPs) in up to 127,282 individuals of six population groups (91% of European population) from the Co...

Importance: Individual variation in statin biotransformation may explain differences in clinical outcomes but remains poorly understood. Objectives: To quantify statin biotransformation phenotypes in cardiology patients and validate predictors of 5-year clinical outcomes in two independent cohorts. Design: SAPhIRE is a multicentre, prospective, obs...

Anthocyanin (ACN) fortification of commonly consumed foods is significant as a dietary strategy against the development of metabolic complications by delivering ACNs at high doses. However, its bioactivity and translated metabolic effects in the presence of varying food matrices and macro-constituents is particularly unclear. This end-to-end study...

Background Two polyclinics in Singapore modified systems and trained health professionals to provide person-centred Care and Support Planning (CSP) for people with diabetes within a clinical trial. We aimed to investigate health professionals’ perspectives on CSP to inform future developments. Methods Qualitative research including 23 semi-structu...

Significance Statement Genome-wide association studies have identified nearly 20 IgA nephropathy susceptibility loci. However, most nonsynonymous coding variants, particularly ones that occur rarely or at a low frequency, have not been well investigated. The authors performed a chip-based association study of IgA nephropathy in 8529 patients with t...

The coding variant (p.Arg192His) in the transcription factor PAX4 is associated with an altered risk for type 2 diabetes (T2D) in East Asian populations. In mice, Pax4 is essential for beta cell formation but its role on human beta cell development and/or function is unknown. Participants carrying the PAX4 p.His192 allele exhibited decreased pancre...

The coding variant (p.Arg192His) in the transcription factor PAX4 is associated with an altered risk for type 2 diabetes (T2D) in East Asian populations. In mice, Pax4 is essential for beta cell formation but its role on human beta cell development and/or function is unknown. Participants carrying the PAX4 p.His192 allele exhibited decreased pancre...

Structural variants (SVs) are significant contributors to inter-individual genetic variation associated with traits and diseases. Current SV studies using whole-genome sequencing (WGS) have a largely Eurocentric composition, with little known about SV diversity in other ancestries particularly from Asia. Here, we present a WGS catalogue of 152,655...

Aims: To assess three well-established type 2 diabetes (T2D) risk prediction models based on fasting plasma glucose (FPG) in Chinese, Malays, and Indians, and to develop simplified risk models based on either FPG or HbA1c. Methods: We used a prospective multiethnic Singapore cohort to evaluate the established models and develop simplified models...

Introduction Prospective data on differences in type two diabetes (T2D) risk between Asian ethnic groups are sparse. We, therefore, compared T2D risk for East (Chinese), South (Indian), and Southeast (Malay) Asians and examined biological factors that may contribute to ethnic differences. Research design and methods We included 7427 adults of Chin...

The molecular mechanisms connecting obesity and cardiometabolic diseases are not fully understood. We evaluated the associations between body mass index (BMI), waist circumference (WC), and ∼5,000 plasma proteins in the Singapore Multi-Ethnic Cohort (MEC1). Among 410 BMI-associated and 385 WC-associated proteins, we identified protein signatures of...

Background Diabetes is a serious public health concern worldwide. Despite public health efforts encouraging early screening and improving knowledge of effective interventions for those at increased risk of type 2 diabetes (T2D), the incorporation of preventative behaviors into an individual’s daily life remains suboptimal. Successfully and accurate...

Sensitivity and plasticity of insulin signaling and glucose uptake in skeletal muscle depends on determinants such as genetic variation and obesity. We collected muscle biopsies and isolated myoblasts from a multi-ethnic cohort of lean South Asians (N=10), lean Chinese (N=10), and obese Chinese (N=10), and analysed the proteome and phosphoproteome...

Background Non-communicable diseases (NCDs) and common mental disorders (CMDs) are the leading causes of death and disability worldwide. Lifestyle interventions via mobile apps and conversational agents present themselves as low-cost, scalable solutions to prevent these conditions. This paper describes the rationale for, and development of, “LvL UP...

Renal defects in maturity onset diabetes of the young 3 (MODY3) patients and Hnf1a -/- mice suggest an involvement of HNF1A in kidney development and/or its function. Although numerous studies have leveraged on Hnf1α -/- mice to infer some transcriptional targets and function of HNF1A in mouse kidneys, species-specific differences obviate a straigh...

The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics¹. Here we examine a large cohort (the INTERVAL study²; n = 50,000 part...

OBJECTIVE The plasma proteome preceding diabetes can improve our understanding of diabetes pathogenesis. RESEARCH DESIGN AND METHODS In 8,923 Atherosclerosis Risk in Communities (ARIC) Study participants (aged 47–70 years, 57% women, 19% Black), we conducted discovery and internal validation for associations of 4,955 plasma proteins with incident...

Precision medicine promises to transform healthcare for groups and individuals through early disease detection, refining diagnoses and tailoring treatments. Analysis of large-scale genomic–phenotypic databases is a critical enabler of precision medicine. Although Asia is home to 60% of the world’s population, many Asian ancestries are under-represe...

This study investigates freeze-dried okra seed flour (OSF) as a functional ingredient to attenuate postprandial blood glucose rise by creating lower glycemic index (GI) rice noodles. Secondary objectives are postprandial gut hormone responses, noodle satiety, and sensory evaluation. Twenty healthy individuals consumed control rice noodle (CON), 10...

One of the promises of precision medicine is to understand and act on inter-individual genetic differences in drug responses. SNPdrug3D contains the complete genomic landscape of missense single nucleotide variants (SNV) across the human proteome and at population-wide level that could affect drug binding. In the Singapore SG10K Health and global g...

Background In 2021, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) validated a new equation for estimated glomerular filtration rate (eGFR). However, this new equation is not ethnic-specific, and prevalence of CKD in Asians is known to differ from other ethnicities. This study evaluates the impact of the 2009 and 2021 creatinine-ba...

Precision medicine is an emerging approach to treatment and disease prevention that relies on linkages between very large datasets of health information that is shared amongst researchers and health professionals. While studies suggest broad support for sharing precision medicine data with researchers at publicly funded institutions, there is reluc...

Background Glycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear and it is unknown whether hypoglycinemia is a cause or consequence of insulin resistance. Objective Using multiple isotopically labeled tracers, we aimed to determine th...

This paper showcases an end-to-end study encompassing the design and prototyping of novel food assemblies using hydrocolloids via microfluidic processing and a detailed assessment of their impact and performance in both in vitro and in vivo contexts. We demonstrated the creation of low-calorie noodle-like food assemblies from mixtures of food hydro...

In an effort to identify disease-causing mechanisms, numerous genome-wide studies across different ancestries have discovered genetic variants influencing type 2 diabetes (T2D) risk. Amongst identified diabetes-associated loci, a PAX4 coding variant (p.Arg192His) is uniquely and reproducibly associated with altered T2D-risk in East Asian population...

The exact clinical course and factors associated with persistent endocrine immune-related adverse events (irAEs) are not well-established. Elucidation of these information will aid irAEs screening and follow-up planning for patients on immunotherapy. We analysed the clinical course of endocrine irAEs including thyroid and pituitary dysfunction and...

Diabetes is a major chronic disease with an excessive healthcare burden on society ¹ . A coding variant (p.Arg192His) in the transcription factor PAX4 is uniquely and reproducibly associated with an altered risk for type 2 diabetes (T2D) in East Asian populations 2–7 , whilst rare PAX4 alleles have been proposed to cause monogenic diabetes ⁸ . In m...

In the past one or two decades, countries across the world have successively implemented different precision medicine (PM) programs, and also cooperated to implement international PM programs. We are now in the era of PM. Singapore's National Precision Medicine (NPM) program, initiated in 2017, is now entering its second phase to generate a large g...

Genetically predicted levels of multi-omic traits can uncover the molecular underpinnings of common phenotypes in a highly efficient manner. Here, we utilised a large cohort (INTERVAL; N=50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, N=3,175; Olink, N=4,822), plasma metabolomics (Metabolon HD4, N=8,153), serum...

Context While Asians have a higher risk of type 2 diabetes (T2D) than Europeans for a given BMI, it remains unclear whether the same markers of metabolic pathways are associated with diabetes. Objective We evaluated associations between metabolic biomarkers and incident T2D in three major Asian ethnic groups (Chinese, Malay, and Indian) and a Euro...

Aims: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. Methods and results: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising...

Background: In 2021, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) validated a new equation for estimated glomerular filtration rate (eGFR) without race as an explanatory variable. Because the prevalence of chronic kidney disease (CKD) in Asians is known to differ from other ethnicities, this manuscript compares prevalence of CKD...

Background: Cardiovascular diseases (CVDs) are a major cause of deaths worldwide, but prospective data on dietary risk factors for CVD in South and Southeast Asian populations are sparse. Objective: We aimed to evaluate the relation between macronutrient and food intakes and incidence of major adverse cardiovascular events (MACEs) in a multi-eth...

Objective Population level data from Asia on amputation rates in people with and without diabetes are extremely limited. Hence it is unclear how the rising diabetes prevalence in Asia has affected the amputation burden. The present study examined national amputation rates in people with and without diabetes in Singapore from 2008 to 2017 in the con...

Background: Branched chain amino acids (BCAA) supplementation is reported to aid in lean mass preservation, which may in turn minimize the reduction in resting metabolic rate (RMR) during weight loss. Our study aimed to examine the effect of BCAA supplementation to a hypocaloric diet on RMR and substrate utilization during a weight loss interventi...

Introduction: There is no study that identified contributions of socio-economic status (SES), lifestyle, and biological risk factors to ethnic differences in T2D risk in Asia’s populous ethnic groups - Chinese, Malays and Indians. Methods: We used data of 7,427 participants from the Multiethnic Cohort, a population-based study of subjects aged ≥21...

Background Hypertriglyceridemia has emerged as a critical coronary artery disease (CAD) risk factor. Rare loss-of-function (LoF) variants in apolipoprotein C-III have been reported to reduce triglycerides (TG) and are cardioprotective in American Indians and Europeans. However, there is a lack of data in other Europeans and non-Europeans. Also, whe...

Background: Precision medicine (PM) programs typically use broad consent. This approach requires maintenance of the social license and public trust. The ultimate success of PM programs will thus likely be contingent upon understanding public expectations about data sharing and establishing appropriate governance structures. There is a lack of data...

Obesity and chronic kidney disease (CKD) are major public health problems worldwide. However, the association between body mass index (BMI) and CKD is inconclusive in Asians. In this meta-analysis, eight population-based studies, from China, India, Russia (Asian), Singapore and South Korea, provided individual-level data (n=50037). CKD was defined...

Background The standard of care for thyroid cancer management is thyroidectomy and adjuvant radioactive iodine (RAI). There is a paucity of clinical tool that quantifies residual thyroid volume reliably for precise adjuvant RAI dosing. Serum thyroglobulin (TG), tumour marker for thyroid cancer, takes 4 weeks for complete clearance due to its long h...

Background Diabetes mellitus (DM) is an important public health concern in Singapore and places a massive burden on health care spending. Tackling chronic diseases such as DM requires innovative strategies to integrate patients' data from diverse sources and use scientific discovery to inform clinical practice that can help better manage the diseas...

Aims/hypothesis: We aimed to evaluate metabolic biomarkers in relation to incident type 2 diabetes (T2D) representing three major ethnic groups in Asia (Chinese, Malay, and Indian) and a European population. Methods: We used data from male and female adult participants of multiple cohorts, including two cohorts from Singapore (n = 6,393 Asians) con...

Aims/hypothesis Diabetes progression and complication risk are different in Asian people compared with those of European ancestry. In this study, we sought to understand the epidemiology of diabetes-related lower extremity complications (DRLECs: symptomatic peripheral arterial disease, ulceration, infection, gangrene) and amputations in a multi-eth...

The prevalence of gestational diabetes mellitus (GDM) is increasing, and only a few mobile health (mHealth) applications are specifically designed to manage GDM. In this mixed-methods study, a follow-up study of a randomized controlled trial (RCT) analyzed a largely automated mHealth application-based lifestyle coaching program to (a) measure the a...

Objectives Using modern food technologies, a novel fibre composition was designed to reduce the glycemic response of white rice while maintaining its organoleptic properties. An increased intake of dietary fibre improves glycemic control and satiety. The incorporation of fibre into staple foods may be a viable dietary strategy against type 2 diabet...

Objectives Sphingolipid concentrations have been associated with risk of type 2 diabetes and cardiovascular diseases. Because sphingolipids can be synthesized de novo from saturated fatty acids (SFA), dietary fatty acids may affect plasma sphingolipid concentrations. We aimed to evaluate dietary fat and protein intakes in relation to circulating sp...

Background High sensitive cardiac troponin assays can be used for prediction of major adverse cardiac events (MACE) in patients with chest pain. Methods We included patients with symptoms suggestive of acute coronary syndrome in the emergency department observation unit. We compared the accuracy of conventional troponin T (cTnT) with high sensitiv...

Heterozygous HNF1A gene mutations can cause maturity onset diabetes of the young 3 (MODY3), characterized by insulin secretion defects. However, specific mechanisms of MODY3 in humans remain unclear due to lack of access to diseased human pancreatic cells. Here, we utilize MODY3 patient-derived human induced pluripotent stem cells (hiPSCs) to study...

We conducted untargeted metabolomics analysis of plasma samples from a cross-sectional case–control study with 30 healthy controls, 30 patients with diabetes mellitus and normal renal function (DM-N), and 30 early diabetic nephropathy (DKD) patients using liquid chromatography-mass spectrometry (LC-MS). We employed two different modes of MS acquisi...

Background Women with a history of gestational diabetes mellitus (GDM) are at an increased risk of developing type 2 diabetes mellitus (T2DM). Lifestyle interventions aimed at postpartum weight loss to reduce T2DM risk have been reported, but poor compliance remains a barrier. Smartphone-based interventions may improve compliance, but data on its u...

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of IC...

The objective was to examine prospectively the association between retinal microvascular signs and development of diabetic kidney disease (DKD) in Asian and White populations. We analysed two population-based cohorts, composing of 1,221 Asians (SEED) and 703 White (WESDR) adults with diabetes. Retinal microvascular signs at baseline included vascul...

Novel staple foods are staple foods that are modified with the purpose of improving their nutritional properties. However, consumers’ acceptance towards novel staple foods remains to be evaluated, especially in Asian populations where staple foods like white rice are a major source of energy. The objective of this study was to explore consumers’ at...

Background/aims Obesity is a well-known risk factor for diabetes, but its association with diabetic retinopathy (DR) is inconclusive, in particular in Asians. We aimed to assess whether body mass index (BMI) is associated with the presence and severity of DR in Asian populations with diabetes. Methods Pooled analysis of individual-level cross-sect...

Sphingolipid concentrations have been associated with risk of type 2 diabetes and cardiovascular diseases. Because sphingolipids can be synthesized de novo from saturated fatty acids (SFA), dietary fatty acids may affect plasma sphingolipid concentrations. We aimed to evaluate dietary fat and protein intakes in relation to circulating sphingolipid...

Background: Branched-chain amino acid (BCAA) supplementation has been shown to increase muscle mass or prevent muscle loss during weight loss. Objective: We aimed to investigate the effects of a BCAA-supplemented hypocaloric diet on lean mass preservation and insulin sensitivity. Methods: A total of 132 Chinese adults (63 men and 69 women aged...

Background Diabetes mellitus (DM) is one of the most common chronic diseases. Individuals with DM are more likely to be hospitalised and stay longer than those without DM. Inpatient hypoglycemia and hyperglycemia, which are associated with adverse outcomes, are common, but can be prevented through hospital quality improvement programs. Methods We...

Background We aimed to examine the ethical concerns Singaporeans have about sharing health-data for precision medicine (PM) and identify suggestions for governance strategies. Just as Asian genomes are under-represented in PM, the views of Asian populations about the risks and benefits of data sharing are under-represented in prior attitudinal rese...