Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Nalagenetics, Singapore, Singapore.
Nat Commun. 2024 Nov 4;15(1):9507. doi: 10.1038/s41467-024-53620-8.
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 SVs from 8392 Singaporeans of East Asian, Southeast Asian and South Asian ancestries, of which ~65% (47,770 SVs) are novel. We show that Asian populations can be stratified by their global SV patterns and identified 42,239 novel SVs that are specific to Asian populations. 52% of these novel SVs are restricted to one of the three major ancestry groups studied (Indian, Chinese or Malay). We uncovered SVs affecting major 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 of 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.
结构变异（SV）是导致个体间遗传变异的重要因素，与特征和疾病有关。目前使用全基因组测序（WGS）的 SV 研究主要以欧洲人为中心，对其他血统（特别是亚洲血统）的 SV 多样性知之甚少。在这里，我们展示了来自东亚、东南亚和南亚血统的 8392 名新加坡人 WGS 目录中的 73035 个 SV，其中约 65%（47770 个 SV）是新的。我们表明，亚洲人群可以根据其全球 SV 模式进行分层，并确定了 42239 个仅存在于所研究的三个主要血统群体（印度、中国或马来）之一的新型 SV。这些新型 SV 的 52%仅限于所研究的三个主要血统群体之一（印度、中国或马来）。我们发现了影响主要临床可操作基因座的 SV。最后，通过鉴定与单核苷酸变异处于连锁不平衡的 SV，我们证明了我们的 SV 目录在亚洲 GWAS 变异的精细映射以及鉴定潜在致病变异中的实用性。这些结果增加了我们对人类群体结构变异的认识，从而减少了当前全球遗传变异参考中影响公平、多样性和包容性的遗传研究中的种族偏见。
