Description

This track shows structural variants (SVs) identified by PacBio HiFi long-read sequencing of 1,027 individuals from the All of Us (AoU) Research Program. Participants self-identified as Black or African American and were sequenced to ~8x coverage. The dataset contains 541,049 SVs (444,524 insertions and 96,525 deletions) on autosomes.

SVs are annotated with population-specific allele frequencies across five ancestry groups (African, Admixed American, East Asian, European, South Asian), gene intersections from curated disease gene lists (OMIM, ACMG, cancer genes), regulatory element overlaps, and associations with eQTLs, GWAS loci, and clinical phenotypes from the AoU electronic health records.

Display Conventions and Configuration

Items are colored by SV type:

• Deletions (DEL) - red
• Insertions (INS) - blue

Filters are available for SV type, SV length, and population-specific allele frequencies. For insertions, the item is placed at the insertion site with a width of 1 bp; for deletions, the item spans the deleted region.

The detail page shows the following annotations when available:

• Population Allele Frequencies: separate frequencies for AFR, AMR, EAS, EUR, and SAS ancestry groups
• Fst: fixation index between African and non-African populations
• Gene Intersections: overlapping OMIM, disease, cancer, and ACMG genes with constraint scores (pLI and LOEUF)
• Regulatory Elements: intersected regulatory elements (e.g. enhancer, promoter)
• Other LR Datasets: whether the SV was also detected in HPRC, HGSVC, or 1KG-ONT long-read datasets
• eQTLs: expression QTL associations with q-values
• GWAS Associations: overlapping GWAS loci with trait, gene, rsID, and LD information
• SV-Trait Associations: associations with clinical phenotypes from AoU electronic health records, including odds ratios and confidence intervals

Methods

PacBio HiFi long-read sequencing was performed on 1,027 AoU participants self-identifying as Black or African American, at a median coverage of ~8x. SV calling was performed using a cohort-level pipeline, producing calls for insertions and deletions. Allele frequencies were computed separately for five ancestry groups. SVs were annotated with gene intersections from OMIM, disease gene panels, cancer gene lists, and ACMG actionable genes, along with regulatory element overlaps and segmental duplication associations.

A scalable imputation workflow was developed to impute over 750,000 SVs into existing short-read whole-genome sequencing datasets. SV-trait associations were tested in 848 AoU participants with matched electronic health records, identifying 291 significant associations across 226 conditions.

Data Access

This track was built from supplementary data (media-2) of the AoU long-read sequencing preprint. Access to the full AoU dataset requires registration through the All of Us Research Hub.

Credits

Thanks to Garimella et al. and the All of Us Research Program for making their structural variant annotations publicly available.

References

Garimella KV, Li Q, Wertz J, Lee SK, Cunial F, Huang Y, Mostovoy Y, Lorig-Roach R, English A, Su H et al. Population-scale Long-read Sequencing in the All of Us Research Program. medRxiv. 2025 Oct 5;. PMID: 41256123; PMC: PMC12622093