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Peer-reviewedCC BYNature Genetics

Genome-wide associations of structural variants with human traits through imputation from long-read assemblies

  • Wei-Yang Bai1,2
  • Shuli Liu1,2
  • Zhongqu Duan1,2
  • Ji-Jian Yang3,4,5
  • Jie Chen6,2
  • Junren Hou1,2
  • Lianfeng Wu6,2
  • Nan Li3
  • Ting Qi1,7,2
  • Jian Yang3,4,5
7 affiliations
  1. 1New Cornerstone Science Laboratory, School of Life Sciences, Westlake University, Hangzhou, China
  2. 2Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China
  3. 3High-Performance Computing Center, Westlake University, Hangzhou, China
  4. 4New Cornerstone Science Laboratory, School of Life Sciences, Westlake University, Hangzhou, China. [email protected]
  5. 5Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China. [email protected]
  6. 6School of Life Sciences, Westlake University, Hangzhou, China
  7. 7Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
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Abstract

Structural variants (SVs) are a major type of genetic variation, yet their role in human traits remains largely uncharacterized, primarily due to challenges in genotyping them on a genome-wide scale in large cohorts. Here we identified 171,233 high-quality, genome-wide SVs from 482 haplotype-resolved genome assemblies derived from PacBio HiFi long-read sequencing of 241 individuals. We developed a reference panel and a web application (ImputeSV) to impute these SVs from single-nucleotide polymorphism (SNP) data and demonstrated high imputation accuracy at both the individual and cohort levels. Using this tool, we imputed 54,578 common SVs (minor allele frequencies (MAFs) ≥1%) in 456,643 UK Biobank (UKB) participants of European ancestry. Through analysis of UKB data and simulations, we estimated that SVs contributed to at least 4.7% of the common genetic variation for complex traits. Genome-wide association analyses of SVs for 2,624 UKB traits identified 17,335 SV-trait associations, including 958 unlikely to be driven by small genetic variants. Our study demonstrates the power of using long-read assemblies for imputing SVs from SNPs, unveils the role of SVs in complex trait variation and provides a catalog of SV associations in the UKB.

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Cite

BibTeXRIS
BibTeX
@article{bai2026genomewide,
  title = {{Genome-wide associations of structural variants with human traits through imputation from long-read assemblies}},
  author = {Wei-Yang Bai and Shuli Liu and Zhongqu Duan and Ji-Jian Yang and Jie Chen and Junren Hou and Lianfeng Wu and Nan Li and Ting Qi and Jian Yang},
  journal = {Nature Genetics},
  year = {2026},
  month = may,
  doi = {10.1038/s41588-026-02612-z},
  url = {https://doi.org/10.1038/s41588-026-02612-z},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Genome-wide associations of structural variants with human traits through imputation from long-read assemblies
AU  - Wei-Yang Bai
AU  - Shuli Liu
AU  - Zhongqu Duan
AU  - Ji-Jian Yang
AU  - Jie Chen
AU  - Junren Hou
AU  - Lianfeng Wu
AU  - Nan Li
AU  - Ting Qi
AU  - Jian Yang
PY  - 2026
DA  - 2026/05/19
JO  - Nature Genetics
DO  - 10.1038/s41588-026-02612-z
UR  - https://doi.org/10.1038/s41588-026-02612-z
AB  - Structural variants (SVs) are a major type of genetic variation, yet their role in human traits remains largely uncharacterized, primarily due to challenges in genotyping them on a genome-wide scale in large cohorts. Here we identified 171,233 high-quality, genome-wide SVs from 482 haplotype-resolved genome assemblies derived from PacBio HiFi long-read sequencing of 241 individuals. We developed a reference panel and a web application (ImputeSV) to impute these SVs from single-nucleotide polymorphism (SNP) data and demonstrated high imputation accuracy at both the individual and cohort levels. Using this tool, we imputed 54,578 common SVs (minor allele frequencies (MAFs) ≥1%) in 456,643 UK Biobank (UKB) participants of European ancestry. Through analysis of UKB data and simulations, we estimated that SVs contributed to at least 4.7% of the common genetic variation for complex traits. Genome-wide association analyses of SVs for 2,624 UKB traits identified 17,335 SV-trait associations, including 958 unlikely to be driven by small genetic variants. Our study demonstrates the power of using long-read assemblies for imputing SVs from SNPs, unveils the role of SVs in complex trait variation and provides a catalog of SV associations in the UKB.
SN  - 1061-4036
SN  - 1546-1718
ER  -