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

Tandem repeats (TRs) are highly polymorphic repetitive DNA sequences that account for approximately 3% of the human genome. Expansions of repeats, i.e., having excess number of TR units, are clinically relevant to more than 40 types of Mendelian disorders, primarily affecting the neurological system. For example, Huntington’s disease is caused by the expansion of CAG repeats located in the HTT gene. However, our understanding of TRs in large-scale populations, particularly among Asians, is limited.

This knowledge gap has hindered further research into the role of TRs in complex diseases. By leveraging the PRECISE-SG100K dataset that includes (i) population-scale whole genome sequencing data and (ii) comprehensive health and well-being questionnaires, along with clinically acquired phenotypes, we aim to comprehensively identify TR variations and their contributions to the aetiology of complex neurological and neurocognitive disorders in Singapore Asian populations.

We will utilize various bioinformatics methods, including TR genotyping tools to characterize TR variations and Genome-Wide Association Studies (GWAS) to explore the relationship between TRs and diseases.

Our research will enhance the understanding of TR variations in Asian populations and potentially stimulate further research into complex diseases from the perspective of TRs, ultimately helping to unravel the genetic mechanisms underlying these conditions.