| Title: | A phenome-wide structural variant map from 467,152 UK Biobank genomes |
| Journal: | Cell |
| Published: | 15 Oct 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42880286/ |
| DOI: | https://doi.org/10.1016/j.cell.2026.09.035 |
Publication 21504
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Abstract
Structural variants (SVs) are large (>50 base pairs) genomic rearrangements that can significantly influence human phenotypes, yet their contribution to health and disease remains undercharacterized. We conducted a phenome-wide association study (PheWAS) of 1.6 million SVs identified in whole-genome sequencing data from 467,152 UK Biobank participants, across 13,322 binary, 2,018 quantitative, and 2,923 plasma protein traits. Of these, 82.25% of SVs were outside the detectable range of prior copy-number variant studies. Protein quantitative trait loci analysis linked 3,467 SVs to 1,690 proteins, with effects dependent on SV type and location. In SV-PheWAS, we detected 28,184 associations with human health outcomes. Notably, we uncovered rare SVs with strong phenotypic effects. Furthermore, we show that at known genome-wide association study loci, 32.21% of associated SVs overlapped functional genomic regions. This study underscores the underestimated role of SVs in human genetics and their potential to advance understanding of human biology and drug discovery.</p>
22 Authors
- Santosh S. Atanur
- Fengyuan Hu
- Haiyi Lou
- Xiaoyin Li
- Xueqing Zoe Zou
- Sean O'Dell
- Sri V.V. Deevi
- Paula Sawczuk
- Karyn Megy
- Zammy Fairhurst-Hunter
- Amanda O'Neill
- AstraZeneca Genomics Initiative
- Lifeng Tian
- Keren Carss
- Jonathan Mitchell
- Stewart MacArthur
- Sebastian Wasilewski
- Ryan S. Dhindsa
- Quanli Wang
- Katherine R. Smith
- Oliver S. Burren
- Slavé Petrovski
1 Application
| Application ID | Title |
|---|---|
| 65851 | Large-scale proteomic profiling to facilitate genetics-guided drug discovery and precision medicine: The UK Biobank - Pharma Proteomics Project (UKB-PPP) |
Enabling scientific discoveries that improve human health