A population-scale map of structural variation in the Japanese population

Structural variants (SVs) are major contributors to the genetic variation underlying human traits and diseases, and they frequently exhibit population-specific patterns. However, previous studies have provided limited coverage of diverse ancestries. Here, using the 1000 Genomes Project data as a population reference, we characterized SVs in Japanese individuals and assessed their potential disease associations. We identified 144,978 SVs, of which 26.8% (38,742 SVs) were novel. SV-based analyses stratified Japanese individuals in the context of global populations and revealed population substructure within Japan, distinguishing the central Hondo cluster from the smaller Ryukyu cluster. We also identified SVs affecting clinically relevant loci. By integrating SVs with single-nucleotide variants, we constructed a Japanese population-specific imputation panel and subsequently identified associations between SVs in the human leukocyte antigen region and primary biliary cholangitis, hepatitis B infection, and steroid-sensitive nephrotic syndrome. These findings advance our understanding of SVs in the Japanese population and provide a baseline resource for future genomic studies of SVs in Japan.