Genetic variants contributing to clonal haematopoiesis across diverse Asian genomes

Age-related acquisition of somatic mutations occurs in all tissues, particularly in bone marrow haematopoietic stem cells (HSC), which is referred to as clonal haematopoiesis (CH). Due to the systemic nature of blood and the immune system it gives rise to, CH confers an increased risk of developing coronary artery and heart diseases, lung and myeloproliferative cancers and worsening prognosis for cancer or infectious diseases, such as COVID-19.

The prevalence and aetiology of CH and related conditions have been mostly studied in populations of Caucasian ancestry. Little is known of CH prevalence and the spectrum of CH driver mutations in Asian populations, or of the prevalence of germline variants (including Asian-specific variants) conferring an increased risk of developing CH.

Using SG100K population-scale clinical-grade whole genome sequencing (WGS) we aim to identify and estimate the prevalence of CH driver mutations in our local populations. Having identified CH-affected individuals, we will then proceed to identify CH risk factor variants. We will also correlate CH status with clinical metadata, measures of ageing as well as disease incidence and other disease-related biomarkers.

To link CH-related phenotypes to cellular and molecular readouts, individuals with CH who have had scRNA-sequencing performed on their peripheral blood, as part of the Asian Immune Diversity Atlas (AIDA), will be analysed to identify cell types, cell states, and gene expression programmes that correlate with CH-related features. In addition, copy number variants (CNVs) inferred from AIDA data at single-cell resolution could corroborate clone size estimates derived from SG100K WGS data.