Flagship Projects

S/N

Flagship Project Title

Team

Aims of Project

1

The SG100K cognitive health programme

Topic: Mental Health

Lead PI: Dr Max Lam, Lee Kong Chian School of Medicine, Institute of Mental Health

Co-Lead PI: Dr Jimmy Lee, Institute of Mental Health

Co-Lead PI: Prof Liu Jianjun, Acting Executive Director, Genome Institute of Singapore

1.       Establish the biological underpinnings for cognitive function in diverse Asian and global populations,

2.       Establish the biological convergence between cognitive function and disease traits, and

3.       Establish epidemiological and genomic risk predictors of cognitive health.

Institutions involved: Lee Kong Chian School of Medicine, Nanyang Technological University, Institute of Mental Health, National Neuroscience Institute, A*STAR Genome Institute of Singapore

2

The SG100K_Med Alliance - clinical genetics researchers united for the analysis of mendelian disease variation in SG100K

Topic: Mendelian Diseases

Lead PI: Dr Lim Weng Khong, Duke-NUS Medical School

Co-Lead PI: Dr Joanne Ngeow, Lee Kong Chian School of Medicine

Co-Lead PI: Dr Saumya Jamuar, KK Women's and Children's Hospital

1.       Seek a deeper understanding of genetic disease burden in major Asian populations through a comprehensive analysis of structural variation and short tandem repeat expansions,

2.       Demonstrate how SG100K data can resolve variants of uncertain significance, and

3.       Explore impact of polygenic backgrounds on penetrance in autosomal dominant conditions for under-represented Asian populations.

Institutions involved: Duke-NUS Medical School, Lee Kong Chian School of Medicine, KK Women's and Children's Hospital, A*STAR Genome Institute of Singapore, Singapore National Eye Centre, Tan Tock Seng Hospital, National University of Singapore, National Heart Centre Singapore, National Neuroscience Institute, Khoo Teck Puat Hospital, Nanyang Technological University

3

Identification of Asian-specific genetic association with fat and lean muscle mass distribution

Topic: Fat and Lean Muscle Mass

Lead PI: Dr Liu Boxiang, National University of Singapore

Co-Lead PI: A/P Sim Xueling, National University of Singapore

Co-Lead PI: Prof Tai E Shyong, National University of Singapore

1.       Perform multi-ethnic meta-analysis of fat and lean muscle mass using SG100K and UKBB datasets,

2.       Mendelian randomisation analysis to identify the contribution of fat and lean muscle mass to cardiometabolic diseases,

3.       Colocalisation analysis to identify risk genes affecting fat and lean muscle mass, and

4.       Conduct functional validation studies of identified genetic loci.

Institutions involved: National University of Singapore

4

HLA alleles and its association with auto-immune diseases and pharmacogenomics in multi-ancestral Asian populations

Topic: Human leukocyte antigen

Lead PI: A/P Sim Xueling, National University of Singapore

Co-Lead PI: Dr Leong Khai Pang, Tan Tock Seng Hospital

Co-Lead PI: Dr Wharton Chan, Duke-NUS Medical School

1.       Generate a high-resolution human leukocyte antigen (HLA) reference panel in Asian populations,

2.       Generate frequencies of HLA alleles and haplotypes in Asian populations for local reference and for global population comparisons, and

3.       Conduct association analyses of HLA alleles in outcomes including auto-immune diseases and pharmacogenomic responses.

Institutions involved: National University of Singapore, Tan Tock Seng Hospital, Duke-NUS Medical School

5

Unravelling the determinants of kidney health in a multi-ethnic Asian population

Topic: Kidney Disease

Lead PI: Dr Yeo See Cheng, Tan Tock Seng Hospital

Co-Lead PI: Prof John Chambers, Lee Kong Chian School of Medicine

1.       Determine prevalence of chronic kidney disease (CKD) among adults

2.       Examine association of CKD with genetic, clinical and socio-behavioural predictors,

3.       Examine relative contribution of key predictors driving differences in CKD risks across different sub-population, and

4.       Develop and validate an integrated risk score for the development of CKD in a representative multi-ethnic Asian population-based cohort in Singapore.

Institutions involved: Tan Tock Seng Hospital, Lee Kong Chian School of Medicine

6

The high variability of tandem repeats offers insights into population diversity and may explain the missing heritability of complex neurological and neurocognitive disorders in Asian populations

Topic: Tandem Repeats

Lead PI: Prof Liu Jianjun, A*STAR Genome Institute of Singapore

Co-Lead PI: Dr Nicolas Bertin, A*STAR Genome Institute of Singapore

Co-Lead PI: Dr Lim Weng Khong, Duke-NUS Medical School

1.       Generate SG100K genome wide tandem repeats (TR) variation catalogue and characterisation their respective prevalence in Asian populations, and

2.       Characterise contributions of TR variations to the aetiology of complex neurological and neurocognitive disorders.

Institutions involved: A*STAR Genome Institute of Singapore, Duke-NUS Medical School, National Neuroscience Institute

7

An integrated pharmacoeconomic-pharmacokinetic framework for prioritising and testing clinically important drug-gene interactions

Topic: Pharmacogenomics

Lead PI: Dr Janice Goh, A*STAR Bioinformatics Institute

Co-Lead PI: A/P Wee Hwee Lin, National University of Singapore

Co-Lead PI: Dr Nicolas Bertin, A*STAR Genome Institute of Singapore

1.       Evaluate the occurrence of known drug-gene interactions based on EHR data and its impact on efficacy and toxicity,

2.       Explore genotype-drug response associations using SG100K and linked EHR datasets augmented by a dedicated pipeline for haplotyping highly polymorphic drug metabolising enzyme CYP2D6, and

3.       Develop a pharmacokinetics-informed framework for evaluating and ranking both known and novel drug-gene sets for clinical action to make dose recommendations

Institutions involved: A*STAR Bioinformatics Institute, National University of Singapore, A*STAR Genome Institute of Singapore

8

Genetic variants contributing to clonal haematopoiesis across diverse Asian genomes

Topic: Clonal haematopoiesis

Lead PI: Prof Ong Sin Tiong, Duke-NUS Medical School

Co-Lead PI: Prof Ashok Venkitaraman, National University of Singapore

Co-Lead PI: Prof Chng Wee Joo, National University of Singapore

Co-Lead PI: Prof John Chambers, Lee Kong Chian School of Medicine

Co-Lead PI: Dr Nicolas Bertin, A*STAR Genome Institute of Singapore

1.       Determine age-related incidence of clonal haematopoiesis (CH) among our three major ancestry groups,

2.       Correlate CH status with clinical metadata, measures of ageing and disease incidence, and disease-related variables including biomarkers,

3.       Discover novel genetic associations with CH,

4.       Integrate functional genomics for novel Asian CH driver mutation discovery and validation, and

5.       Correlate CH status with cell clusters and gene expression signatures in the AIDA scRNA-seq dataset.

Institutions involved: Duke-NUS Medical School, National University of Singapore, Lee Kong Chian School of Medicine, A*STAR Genome Institute of Singapore, National University Hospital, Singapore General Hospital