A Genomics England haplotype reference panel and imputation of UK Biobank
We built a reference panel with 342 million autosomal variants using 78,195 individuals from the Genomics England (GEL) dataset, achieving a phasing switch error rate of 0.18% for European samples and imputation quality of r<sup>2</sup> = 0.75 for variants with minor allele frequencies as low as 2 × 10<sup>-4</sup> in white British samples. The GEL-imputed UK Biobank genome-wide association analysis identified 70% of associations found by direct exome sequencing (P < 2.18 × 10<sup>-11</sup>), while extending testing of rare variants to the entire genome. Coding variants dominated the rare-variant genome-wide association results, implying less disruptive effects of rare non-coding variants.
Authors
- Anna C. Need (ORCID: https://orcid.org/0000-0003-3955-8207)
- Pier Francesco Palamara (ORCID: https://orcid.org/0000-0002-7999-1972)
- Simone Rubinacci (ORCID: https://orcid.org/0000-0002-7725-4813)
- Loukas Moutsianas (ORCID: https://orcid.org/0000-0001-5453-345X)
- Sile Hu (ORCID: https://orcid.org/0000-0002-8437-7387)
- Alexander Stuckey (ORCID: https://orcid.org/0000-0001-8636-737X)
- Jonathan Marchini (ORCID: https://orcid.org/0000-0003-0610-8322)
- Simon Myers (ORCID: https://orcid.org/0000-0002-2585-9626)
- Sinan Shi (ORCID: https://orcid.org/0000-0001-6935-0429)
- Mark J. Caulfield (ORCID: https://orcid.org/0000-0001-9295-3594)
Institutions
- Harvard University (US)
- Queen Mary University of London (GB)
- Regeneron (United States) (US)
- University of Oxford (GB)
- Novo Nordisk (United Kingdom) (GB)
- Genomics England (GB)
- Science Oxford (GB)
Publication Details
- Journal
- Nature Genetics
- Published
- 2024-08-12
- DOI
- https://doi.org/10.1038/s41588-024-01868-7
- Citations
- 21
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 11.56
Funders
- Wellcome Trust
- Barts Charity
- Cancer Research UK
- National Institute for Health and Care Research
- Department of Health and Social Care
- Medical Research Council