Journal article
Flexible read-aware genotype imputation from sequence using biobank sized reference panels
- Abstract:
- Inexpensive and accurate genotyping methods are essential to modern genomics and health risk prediction. Here we introduce QUILT2, a scalable and read-aware imputation method that can efficiently use biobank scale haplotype reference panels. This allows for fast and accurate imputation using short reads, as well as long reads (e.g. Oxford Nanopore Technologies (ONT) 1X, r2 = 0.937 at common SNPs), linked-reads and ancient DNA. In addition, QUILT2 contains a methodological innovation that is designed to enable imputation of the maternal and fetal genome using cell free non-invasive prenatal testing (NIPT) data. Using a UK Biobank reference panel and simulated NIPT data, we see accurate imputation of the mother (0.25X, r2 = 0.966, common SNPs) and modest imputation of the fetus (0.25X, r2 = 0.465, fetal fraction of 10%) at low coverage, with fetal imputation accuracy rising with coverage (4.0X, fetal r2 = 0.894). We show using simulated data that this could enable both GWAS and PRS for the mother and fetus, which could create clinical opportunities, and if phenotypes can be collected alongside clinical NIPT, the potential for large GWAS.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 927.6KB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-025-67218-1
Authors
+ Novo Nordisk Foundation
More from this funder
- Funder identifier:
- https://ror.org/04txyc737
- Funding agency for:
- Li, Z
- Albrechtsen, A
- Grant:
- NNF20OC0061343
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 17
- Issue:
- 1
- Article number:
- 524
- Publication date:
- 2025-12-13
- Acceptance date:
- 2025-11-25
- DOI:
- EISSN:
-
2041-1723
- ISSN:
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2041-1723
- Language:
-
English
- Pubs id:
-
2350949
- UUID:
-
uuid_37e11d8a-67a3-455b-a0cb-f6453691da00
- Local pid:
-
pubs:2350949
- Source identifiers:
-
W4417321304
- Deposit date:
-
2025-12-18
- ARK identifier:
Terms of use
- Copyright holder:
- Li et al.
- Copyright date:
- 2025
- Rights statement:
- © The Author(s) 2025. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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