| Title: | Accurate rare variant phasing of whole-genome and whole-exome sequencing data in the UK Biobank |
| Journal: | Nature Genetics |
| Published: | 29 Jun 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37386248/ |
| DOI: | https://doi.org/10.1038/s41588-023-01415-w |
| URL: | https://www.nature.com/articles/s41588-023-01415-w.pdf |
| Citations: | 48 (47 in last 2 years) as of 8 Aug 2024 |
Publication 7739
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Phasing involves distinguishing the two parentally inherited copies of each chromosome into haplotypes. Here, we introduce SHAPEIT5, a new phasing method that quickly and accurately processes large sequencing datasets and applied it to UK Biobank (UKB) whole-genome and whole-exome sequencing data. We demonstrate that SHAPEIT5 phases rare variants with low switch error rates of below 5% for variants present in just 1 sample out of 100,000. Furthermore, we outline a method for phasing singletons, which, although less precise, constitutes an important step towards future developments. We then demonstrate that the use of UKB as a reference panel improves the accuracy of genotype imputation, which is even more pronounced when phased with SHAPEIT5 compared with other methods. Finally, we screen the UKB data for loss-of-function compound heterozygous events and identify 549 genes where both gene copies are knocked out. These genes complement current knowledge of gene essentiality in the human genome.4 Authors
- Robin J. Hofmeister
- Diogo M. Ribeiro
- Simone Rubinacci
- Olivier Delaneau
1 Application
| Application ID | Title |
|---|---|
| 66995 | Prediction of haplotypes, genotypes, parental-of-origin and applications in biobanks. |
Enabling scientific discoveries that improve human health