Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Huang, Jie, Howie, Bryan, McCarthy, Shane, Memari, Yasin, Walter, Klaudia, Min, Josine L., Danecek, Petr, Malerba, Giovanni, Trabetti, Elisabetta, Zheng, Hou-Feng, Gambaro, Giovanni, Richards, J. Brent, Durbin, Richard, Timpson, Nicholas J., Marchini, Jonathan, Soranzo, Nicole, UK10K Consortium, Evans, David M., Kemp, John P., Visscher, Peter M. and Yang, Jian (2015) Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel. Nature Communications, 6 8111.1-8111.9. doi:10.1038/ncomms9111

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Author Huang, Jie
Howie, Bryan
McCarthy, Shane
Memari, Yasin
Walter, Klaudia
Min, Josine L.
Danecek, Petr
Malerba, Giovanni
Trabetti, Elisabetta
Zheng, Hou-Feng
Gambaro, Giovanni
Richards, J. Brent
Durbin, Richard
Timpson, Nicholas J.
Marchini, Jonathan
Soranzo, Nicole
UK10K Consortium
Evans, David M.
Kemp, John P.
Visscher, Peter M.
Yang, Jian
Title Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2015-09-14
Year available 2015
Sub-type Article (original research)
DOI 10.1038/ncomms9111
Open Access Status DOI
Volume 6
Start page 8111.1
End page 8111.9
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
1600 Chemistry
3100 Physics and Astronomy
Abstract Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID WT091310
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 50 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 53 times in Scopus Article | Citations
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