Send to

Choose Destination
Nat Commun. 2015 Sep 14;6:8111. doi: 10.1038/ncomms9111.

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

Collaborators (223)

Al Turki S, Amuzu A, Anderson CA, Anney R, Antony D, Artigas MS, Ayub M, Bala S, Barrett JC, Barroso I, Beales P, Benn M, Bentham J, Bhattacharya S, Birney E, Blackwood D, Bobrow M, Bochukova E, Bolton PF, Bounds R, Boustred C, Breen G, Calissano M, Carss K, Casas JP, Chambers JC, Charlton R, Chatterjee K, Chen L, Ciampi A, Cirak S, Clapham P, Clement G, Coates G, Cocca M, Collier DA, Cosgrove C, Cox T, Craddock N, Crooks L, Curran S, Curtis D, Daly A, Day IN, Day-Williams A, Dedoussis G, Down T, Du Y, van Duijn CM, Dunham I, Edkins S, Ekong R, Ellis P, Evans DM, Farooqi IS, Fitzpatrick DR, Flicek P, Floyd J, Foley AR, Franklin CS, Futema M, Gallagher L, Gasparini P, Gaunt TR, Geihs M, Geschwind D, Greenwood C, Griffin H, Grozeva D, Guo X, Guo X, Gurling H, Hart D, Hendricks AE, Holmans P, Huang L, Hubbard T, Humphries SE, Hurles ME, Hysi P, Iotchkova V, Isaacs A, Jackson DK, Jamshidi Y, Johnson J, Joyce C, Karczewski KJ, Kaye J, Keane T, Kemp JP, Kennedy K, Kent A, Keogh J, Khawaja F, Kleber ME, van Kogelenberg M, Kolb-Kokocinski A, Kooner JS, Lachance G, Langenberg C, Langford C, Lawson D, Lee I, van Leeuwen EM, Lek M, Li R, Li Y, Liang J, Lin H, Liu R, Lönnqvist J, Lopes LR, Lopes M, Luan J, MacArthur DG, Mangino M, Marenne G, März W, Maslen J, Matchan A, Mathieson I, McGuffin P, McIntosh AM, McKechanie AG, McQuillin A, Metrustry S, Migone N, Mitchison HM, Moayyeri A, Morris J, Morris R, Muddyman D, Muntoni F, Nordestgaard BG, Northstone K, O'Donovan MC, O'Rahilly S, Onoufriadis A, Oualkacha K, Owen MJ, Palotie A, Panoutsopoulou K, Parker V, Parr JR, Paternoster L, Paunio T, Payne F, Payne SJ, Perry JR, Pietilainen O, Plagnol V, Pollitt RC, Povey S, Quail MA, Quaye L, Raymond L, Rehnström K, Ridout CK, Ring S, Ritchie GR, Roberts N, Robinson RL, Savage DB, Scambler P, Schiffels S, Schmidts M, Schoenmakers N, Scott RH, Scott RA, Semple RK, Serra E, Sharp SI, Shaw A, Shihab HA, Shin SY, Skuse D, Small KS, Smee C, Smith GD, Southam L, Spasic-Boskovic O, Spector TD, St Clair D, St Pourcain B, Stalker J, Stevens E, Sun J, Surdulescu G, Suvisaari J, Syrris P, Tachmazidou I, Taylor R, Tian J, Tobin MD, Toniolo D, Traglia M, Tybjaerg-Hansen A, Valdes AM, Vandersteen AM, Varbo A, Vijayarangakannan P, Visscher PM, Wain LV, Walters JT, Wang G, Wang J, Wang Y, Ward K, Wheeler E, Whincup P, Whyte T, Williams HJ, Williamson KA, Wilson C, Wilson SG, Wong K, Xu C, Yang J, Zaza G, Zeggini E, Zhang F, Zhang P, Zhang W.

Author information

The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.
Adaptive Biotechnologies Corporation, Seattle Washington 98102, USA.
MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Clifton, Bristol BS8 2BN, UK.
Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, 37134, Italy.
Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2.
Department of Medicine, McGill University, Montreal, Quebec, Canada H3A 1B1.
Department of Human Genetics, McGill University, Montreal, Quebec, Canada H3A 1B1.
Division of Nephrology and Dialysis, Institute of Internal Medicine, Renal Program, Columbus-Gemelli University Hospital, Catholic University, Rome, Italy.
The Department of Twin Research &Genetic Epidemiology, King's College London, St Thomas' Campus, Lambeth Palace Road, London SE1 7EH, UK.
Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK.
Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
Department of Haematology, University of Cambridge, Long Road, Cambridge CB2 0PT, UK.


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center