A Catalogue of Structural Variation across Ancestrally Diverse Asian Genomes

Abstract

Abstract 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 SVs from 8,392 Singaporeans of East Asian, Southeast Asian and South Asian ancestries, of which ~75% (113,446 SVs) are novel. We show that Asian populations can be stratified by their global SV patterns and identified 82,003 novel SVs that are specific to Asian populations. 38% of these novel SVs are restricted to one of the three major ancestry groups studied (Indian, Chinese or Malay). We uncovered SVs affecting ACMG-defined clinically actionable loci. Lastly, by identifying SVs in linkage disequilibrium with single-nucleotide variants, we demonstrate the utility of our SV catalogue in the fine-mapping of Asian GWAS variants and identification potential causative variants. These results augment our knowledge of structural variation across human populations, thereby reducing current ancestry biases in global references of genetic variation afflicting equity, diversity and inclusion in genetic research.