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

Jie Huang; Bryan Howie; Shane Mccarthy; Yasin Memari; Klaudia Walter; Josine L. Min; Petr Danecek; Giovanni Malerba; Elisabetta Trabetti; Hou-feng Zheng; Saeed Al Turki; Antoinette Amuzu; Carl A. Anderson; Richard Anney; Dinu Antony; María Soler Artigas; Muhammad Ayub; Senduran Bala; Jeffrey C. Barrett; Inês Barroso; Phil Beales; Marianne Benn; Jamie Bentham; Shoumo Bhattacharya; Ewan Birney; Douglas Blackwood; Martin Bobrow; Elena Bochukova; Patrick F. Bolton; Rebecca Bounds; Chris Boustred; Gerome Breen; Mattia Calissano; Keren Carss; Juan Pablo Casas; John C. Chambers; Ruth Charlton; Krishna Chatterjee; Lu Chen; Antonio Ciampi; Sebahattin Cirak; Peter Clapham; Gail Clement; Guy Coates; Massimiliano Cocca; David A. Collier; Catherine Cosgrove; Tony Cox; Nick Craddock; Lucy Crooks; Sarah Curran; David Curtis; Allan Daly; Ian N. M. Day; Aaron Day-williams; George Dedoussis; Thomas Down; Yuanping Du; Cornelia M. Van Duijn; Ian Dunham; Sarah Edkins; Rosemary Ekong; Peter Ellis; David M. Evans; I. Sadaf Farooqi; David R. Fitzpatrick; Paul Flicek; James Floyd; A. Reghan Foley; Christopher S. Franklin; Marta Futema; Louise Gallagher; Paolo Gasparini; Tom R. Gaunt; Matthias Geihs; Daniel Geschwind; Celia Greenwood; Heather Griffin; Detelina Grozeva; Xiaosen Guo; Xueqin Guo; Hugh Gurling; Deborah Hart; Audrey E. Hendricks; Peter Holmans; Liren Huang; Tim Hubbard; Steve E. Humphries; Matthew E. Hurles; Pirro Hysi; Valentina Iotchkova; Aaron Isaacs; David K. Jackson; Yalda Jamshidi; Jon Johnson; Chris Joyce; Konrad J. Karczewski; Jane Kaye; Thomas Keane; John P. Kemp; Karen Kennedy; Alastair Kent; Julia Keogh; Farrah Khawaja; Marcus E. Kleber; Margriet Van Kogelenberg; Anja Kolb-kokocinski; Jaspal S. Kooner; Genevieve Lachance; Claudia Langenberg; Cordelia Langford; Daniel Lawson; Irene Lee; Elisabeth M. Van Leeuwen; Monkol Lek; Rui Li; Yingrui Li; Jieqin Liang; Hong Lin; Ryan Liu; Jouko Lönnqvist; Luis R. Lopes; Margarida Lopes; Jian'an Luan; Daniel G. Macarthur; Massimo Mangino; Gaëlle Marenne; Winfried März; John Maslen; Angela Matchan; Iain Mathieson; Peter Mcguffin; Andrew M. Mcintosh; Andrew G. Mckechanie; Andrew Mcquillin; Sarah Metrustry; Nicola Migone; Hannah M. Mitchison; Alireza Moayyeri; James Morris; Richard Morris; Dawn Muddyman; Francesco Muntoni; Børge Nordestgaard; Kate Northstone; Michael C. O'donovan; Stephen O'rahilly; Alexandros Onoufriadis; Karim Oualkacha; Michael J. Owen; Aarno Palotie; Kalliope Panoutsopoulou; Victoria Parker; Jeremy R. Parr; Lavinia Paternoster; Tiina Paunio; Felicity Payne; Stewart J. Payne; John R. B. Perry; Olli Pietilainen; Vincent Plagnol; Rebecca C. Pollitt; Sue Povey; Michael A. Quail; Lydia Quaye; Lucy Raymond; Karola Rehnström; Cheryl K. Ridout; Susan Ring; Graham R. S. Ritchie; Nicola Roberts; Rachel L. Robinson; David B. Savage; Peter Scambler; Stephan Schiffels; Miriam Schmidts; Nadia Schoenmakers; Richard H. Scott; Robert A. Scott; Robert K. Semple; Eva Serra; Sally I. Sharp; Adam Shaw; Hashem A. Shihab; So-youn Shin; David Skuse; Kerrin S. Small; Carol Smee; George Davey Smith; Lorraine Southam; Olivera Spasic-boskovic; Timothy D. Spector; David St Clair; Beate St Pourcain; Jim Stalker; Elizabeth Stevens; Jianping Sun; Gabriela Surdulescu; Jaana Suvisaari; Petros Syrris; Ioanna Tachmazidou; Rohan Taylor; Jing Tian; Martin D. Tobin; Daniela Toniolo; Michela Traglia; Anne Tybjærg-Hansen; Ana M. Valdes; Anthony M. Vandersteen; Anette Varbo; Parthiban Vijayarangakannan; Peter M. Visscher; Louise V. Wain; James T. R. Walters; Guangbiao Wang; Jun Wang; Yu Wang; Kirsten Ward; Eleanor Wheeler; Peter Whincup; Tamieka Whyte; Hywel J. Williams; Kathleen A. Williamson; Crispian Wilson; Scott G. Wilson; Kim Wong; Changjiang Xu; Jian Yang; Gianluigi Zaza; Eleftheria Zeggini; Feng Zhang; Pingbo Zhang; Weihua Zhang; Giovanni Gambaro; J. Brent Richards; Richard Durbin; Nicholas J. Timpson; Jonathan Marchini; Nicole Soranzo

doi:10.1038/ncomms9111

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

Jie Huang, Bryan Howie, Shane Mccarthy, Yasin Memari, Klaudia Walter, Josine L. Min, Petr Danecek, Giovanni Malerba, Elisabetta Trabetti, Hou-feng Zheng, Saeed Al Turki, Antoinette Amuzu, Carl A. Anderson, Richard Anney, Dinu Antony, María Soler Artigas, Muhammad Ayub, Senduran Bala, Jeffrey C. Barrett, Inês BarrosoPhil Beales, Marianne Benn, Jamie Bentham, Shoumo Bhattacharya, Ewan Birney, Douglas Blackwood, Martin Bobrow, Elena Bochukova, Patrick F. Bolton, Rebecca Bounds, Chris Boustred, Gerome Breen, Mattia Calissano, Keren Carss, Juan Pablo Casas, John C. Chambers, Ruth Charlton, Krishna Chatterjee, Lu Chen, Antonio Ciampi, Sebahattin Cirak, Peter Clapham, Gail Clement, Guy Coates, Massimiliano Cocca, David A. Collier, Catherine Cosgrove, Tony Cox, Nick Craddock, Lucy Crooks, Sarah Curran, David Curtis, Allan Daly, Ian N. M. Day, Aaron Day-williams, George Dedoussis, Thomas Down, Yuanping Du, Cornelia M. Van Duijn, Ian Dunham, Sarah Edkins, Rosemary Ekong, Peter Ellis, David M. Evans, I. Sadaf Farooqi, David R. Fitzpatrick, Paul Flicek, James Floyd, A. Reghan Foley, Christopher S. Franklin, Marta Futema, Louise Gallagher, Paolo Gasparini, Tom R. Gaunt, Matthias Geihs, Daniel Geschwind, Celia Greenwood, Heather Griffin, Detelina Grozeva, Xiaosen Guo, Xueqin Guo, Hugh Gurling, Deborah Hart, Audrey E. Hendricks, Peter Holmans, Liren Huang, Tim Hubbard, Steve E. Humphries, Matthew E. Hurles, Pirro Hysi, Valentina Iotchkova, Aaron Isaacs, David K. Jackson, Yalda Jamshidi, Jon Johnson, Chris Joyce, Konrad J. Karczewski, Jane Kaye, Thomas Keane, John P. Kemp, Karen Kennedy, Alastair Kent, Julia Keogh, Farrah Khawaja, Marcus E. Kleber, Margriet Van Kogelenberg, Anja Kolb-kokocinski, Jaspal S. Kooner, Genevieve Lachance, Claudia Langenberg, Cordelia Langford, Daniel Lawson, Irene Lee, Elisabeth M. Van Leeuwen, Monkol Lek, Rui Li, Yingrui Li, Jieqin Liang, Hong Lin, Ryan Liu, Jouko Lönnqvist, Luis R. Lopes, Margarida Lopes, Jian'an Luan, Daniel G. Macarthur, Massimo Mangino, Gaëlle Marenne, Winfried März, John Maslen, Angela Matchan, Iain Mathieson, Peter Mcguffin, Andrew M. Mcintosh, Andrew G. Mckechanie, Andrew Mcquillin, Sarah Metrustry, Nicola Migone, Hannah M. Mitchison, Alireza Moayyeri, James Morris, Richard Morris, Dawn Muddyman, Francesco Muntoni, Børge Nordestgaard, Kate Northstone, Michael C. O'donovan, Stephen O'rahilly, Alexandros Onoufriadis, Karim Oualkacha, Michael J. Owen, Aarno Palotie, Kalliope Panoutsopoulou, Victoria Parker, Jeremy R. Parr, Lavinia Paternoster, Tiina Paunio, Felicity Payne, Stewart J. Payne, John R. B. Perry, Olli Pietilainen, Vincent Plagnol, Rebecca C. Pollitt, Sue Povey, Michael A. Quail, Lydia Quaye, Lucy Raymond, Karola Rehnström, Cheryl K. Ridout, Susan Ring, Graham R. S. Ritchie, Nicola Roberts, Rachel L. Robinson, David B. Savage, Peter Scambler, Stephan Schiffels, Miriam Schmidts, Nadia Schoenmakers, Richard H. Scott, Robert A. Scott, Robert K. Semple, Eva Serra, Sally I. Sharp, Adam Shaw, Hashem A. Shihab, So-youn Shin, David Skuse, Kerrin S. Small, Carol Smee, George Davey Smith, Lorraine Southam, Olivera Spasic-boskovic, Timothy D. Spector, David St Clair, Beate St Pourcain, Jim Stalker, Elizabeth Stevens, Jianping Sun, Gabriela Surdulescu, Jaana Suvisaari, Petros Syrris, Ioanna Tachmazidou, Rohan Taylor, Jing Tian, Martin D. Tobin, Daniela Toniolo, Michela Traglia, Anne Tybjærg-Hansen, Ana M. Valdes, Anthony M. Vandersteen, Anette Varbo, Parthiban Vijayarangakannan, Peter M. Visscher, Louise V. Wain, James T. R. Walters, Guangbiao Wang, Jun Wang, Yu Wang, Kirsten Ward, Eleanor Wheeler, Peter Whincup, Tamieka Whyte, Hywel J. Williams, Kathleen A. Williamson, Crispian Wilson, Scott G. Wilson, Kim Wong, Changjiang Xu, Jian Yang, Gianluigi Zaza, Eleftheria Zeggini, Feng Zhang, Pingbo Zhang, Weihua Zhang, Giovanni Gambaro, J. Brent Richards, Richard Durbin, Nicholas J. Timpson, Jonathan Marchini, Nicole Soranzo

136 Citationer (Scopus)

92 Downloads (Pure)

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.

Originalsprog	Engelsk
Artikelnummer	8111
Tidsskrift	Nature Communications
Vol/bind	6
Antal sider	9
ISSN	2041-1723
DOI	https://doi.org/10.1038/ncomms9111
Status	Udgivet - 14 sep. 2015

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10.1038/ncomms9111

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panelForlagets udgivne version, 486 KB

Citationsformater

Huang, J., Howie, B., Mccarthy, S., Memari, Y., Walter, K., Min, J. L., Danecek, P., Malerba, G., Trabetti, E., Zheng, H., Al Turki, S., Amuzu, A., Anderson, C. A., Anney, R., Antony, D., Artigas, M. S., Ayub, M., Bala, S., Barrett, J. C., ... Soranzo, N. (2015). Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel. Nature Communications, 6, Artikel 8111. https://doi.org/10.1038/ncomms9111

Huang, J, Howie, B, Mccarthy, S, Memari, Y, Walter, K, Min, JL, Danecek, P, Malerba, G, Trabetti, E, Zheng, H, 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, Pablo Casas, J, 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, INM, 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, B, 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, JRB, Pietilainen, O, Plagnol, V, Pollitt, RC, Povey, S, Quail, MA, Quaye, L, Raymond, L, Rehnström, K, Ridout, CK, Ring, S, Ritchie, GRS, 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, S, 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, Tybjærg-Hansen, A, Valdes, AM, Vandersteen, AM, Varbo, A, Vijayarangakannan, P, Visscher, PM, Wain, LV, Walters, JTR, 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, Gambaro, G, Richards, JB, Durbin, R, Timpson, NJ, Marchini, J & Soranzo, N 2015, 'Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel', Nature Communications, bind 6, 8111. https://doi.org/10.1038/ncomms9111

@article{6045338d2ebd4fdb82cdab133f755000,

title = "Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel",

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.",

author = "Jie Huang and Bryan Howie and Shane Mccarthy and Yasin Memari and Klaudia Walter and Min, {Josine L.} and Petr Danecek and Giovanni Malerba and Elisabetta Trabetti and Hou-feng Zheng and {Al Turki}, Saeed and Antoinette Amuzu and Anderson, {Carl A.} and Richard Anney and Dinu Antony and Artigas, {Mar{\'i}a Soler} and Muhammad Ayub and Senduran Bala and Barrett, {Jeffrey C.} and In{\^e}s Barroso and Phil Beales and Marianne Benn and Jamie Bentham and Shoumo Bhattacharya and Ewan Birney and Douglas Blackwood and Martin Bobrow and Elena Bochukova and Bolton, {Patrick F.} and Rebecca Bounds and Chris Boustred and Gerome Breen and Mattia Calissano and Keren Carss and {Pablo Casas}, Juan and Chambers, {John C.} and Ruth Charlton and Krishna Chatterjee and Lu Chen and Antonio Ciampi and Sebahattin Cirak and Peter Clapham and Gail Clement and Guy Coates and Massimiliano Cocca and Collier, {David A.} and Catherine Cosgrove and Tony Cox and Nick Craddock and Lucy Crooks and Sarah Curran and David Curtis and Allan Daly and Day, {Ian N. M.} and Aaron Day-williams and George Dedoussis and Thomas Down and Yuanping Du and {Van Duijn}, {Cornelia M.} and Ian Dunham and Sarah Edkins and Rosemary Ekong and Peter Ellis and Evans, {David M.} and Farooqi, {I. Sadaf} and Fitzpatrick, {David R.} and Paul Flicek and James Floyd and Foley, {A. Reghan} and Franklin, {Christopher S.} and Marta Futema and Louise Gallagher and Paolo Gasparini and Gaunt, {Tom R.} and Matthias Geihs and Daniel Geschwind and Celia Greenwood and Heather Griffin and Detelina Grozeva and Xiaosen Guo and Xueqin Guo and Hugh Gurling and Deborah Hart and Hendricks, {Audrey E.} and Peter Holmans and Liren Huang and Tim Hubbard and Humphries, {Steve E.} and Hurles, {Matthew E.} and Pirro Hysi and Valentina Iotchkova and Aaron Isaacs and Jackson, {David K.} and Yalda Jamshidi and Jon Johnson and Chris Joyce and Karczewski, {Konrad J.} and Jane Kaye and Thomas Keane and Kemp, {John P.} and Karen Kennedy and Alastair Kent and Julia Keogh and Farrah Khawaja and Kleber, {Marcus E.} and {Van Kogelenberg}, Margriet and Anja Kolb-kokocinski and Kooner, {Jaspal S.} and Genevieve Lachance and Claudia Langenberg and Cordelia Langford and Daniel Lawson and Irene Lee and {Van Leeuwen}, {Elisabeth M.} and Monkol Lek and Rui Li and Yingrui Li and Jieqin Liang and Hong Lin and Ryan Liu and Jouko L{\"o}nnqvist and Lopes, {Luis R.} and Margarida Lopes and Jian'an Luan and Macarthur, {Daniel G.} and Massimo Mangino and Ga{\"e}lle Marenne and Winfried M{\"a}rz and John Maslen and Angela Matchan and Iain Mathieson and Peter Mcguffin and Mcintosh, {Andrew M.} and Mckechanie, {Andrew G.} and Andrew Mcquillin and Sarah Metrustry and Nicola Migone and Mitchison, {Hannah M.} and Alireza Moayyeri and James Morris and Richard Morris and Dawn Muddyman and Francesco Muntoni and B{\o}rge Nordestgaard and Kate Northstone and O'donovan, {Michael C.} and Stephen O'rahilly and Alexandros Onoufriadis and Karim Oualkacha and Owen, {Michael J.} and Aarno Palotie and Kalliope Panoutsopoulou and Victoria Parker and Parr, {Jeremy R.} and Lavinia Paternoster and Tiina Paunio and Felicity Payne and Payne, {Stewart J.} and Perry, {John R. B.} and Olli Pietilainen and Vincent Plagnol and Pollitt, {Rebecca C.} and Sue Povey and Quail, {Michael A.} and Lydia Quaye and Lucy Raymond and Karola Rehnstr{\"o}m and Ridout, {Cheryl K.} and Susan Ring and Ritchie, {Graham R. S.} and Nicola Roberts and Robinson, {Rachel L.} and Savage, {David B.} and Peter Scambler and Stephan Schiffels and Miriam Schmidts and Nadia Schoenmakers and Scott, {Richard H.} and Scott, {Robert A.} and Semple, {Robert K.} and Eva Serra and Sharp, {Sally I.} and Adam Shaw and Shihab, {Hashem A.} and So-youn Shin and David Skuse and Small, {Kerrin S.} and Carol Smee and Smith, {George Davey} and Lorraine Southam and Olivera Spasic-boskovic and Spector, {Timothy D.} and {St Clair}, David and {St Pourcain}, Beate and Jim Stalker and Elizabeth Stevens and Jianping Sun and Gabriela Surdulescu and Jaana Suvisaari and Petros Syrris and Ioanna Tachmazidou and Rohan Taylor and Jing Tian and Tobin, {Martin D.} and Daniela Toniolo and Michela Traglia and Anne Tybj{\ae}rg-Hansen and Valdes, {Ana M.} and Vandersteen, {Anthony M.} and Anette Varbo and Parthiban Vijayarangakannan and Visscher, {Peter M.} and Wain, {Louise V.} and Walters, {James T. R.} and Guangbiao Wang and Jun Wang and Yu Wang and Kirsten Ward and Eleanor Wheeler and Peter Whincup and Tamieka Whyte and Williams, {Hywel J.} and Williamson, {Kathleen A.} and Crispian Wilson and Wilson, {Scott G.} and Kim Wong and Changjiang Xu and Jian Yang and Gianluigi Zaza and Eleftheria Zeggini and Feng Zhang and Pingbo Zhang and Weihua Zhang and Giovanni Gambaro and Richards, {J. Brent} and Richard Durbin and Timpson, {Nicholas J.} and Jonathan Marchini and Nicole Soranzo",

year = "2015",

month = sep,

day = "14",

doi = "10.1038/ncomms9111",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

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TY - JOUR

T1 - Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

AU - Huang, Jie

AU - Howie, Bryan

AU - Mccarthy, Shane

AU - Memari, Yasin

AU - Walter, Klaudia

AU - Min, Josine L.

AU - Danecek, Petr

AU - Malerba, Giovanni

AU - Trabetti, Elisabetta

AU - Zheng, Hou-feng

AU - Al Turki, Saeed

AU - Amuzu, Antoinette

AU - Anderson, Carl A.

AU - Anney, Richard

AU - Antony, Dinu

AU - Artigas, María Soler

AU - Ayub, Muhammad

AU - Bala, Senduran

AU - Barrett, Jeffrey C.

AU - Barroso, Inês

AU - Beales, Phil

AU - Benn, Marianne

AU - Bentham, Jamie

AU - Bhattacharya, Shoumo

AU - Birney, Ewan

AU - Blackwood, Douglas

AU - Bobrow, Martin

AU - Bochukova, Elena

AU - Bolton, Patrick F.

AU - Bounds, Rebecca

AU - Boustred, Chris

AU - Breen, Gerome

AU - Calissano, Mattia

AU - Carss, Keren

AU - Pablo Casas, Juan

AU - Chambers, John C.

AU - Charlton, Ruth

AU - Chatterjee, Krishna

AU - Chen, Lu

AU - Ciampi, Antonio

AU - Cirak, Sebahattin

AU - Clapham, Peter

AU - Clement, Gail

AU - Coates, Guy

AU - Cocca, Massimiliano

AU - Collier, David A.

AU - Cosgrove, Catherine

AU - Cox, Tony

AU - Craddock, Nick

AU - Crooks, Lucy

AU - Curran, Sarah

AU - Curtis, David

AU - Daly, Allan

AU - Day, Ian N. M.

AU - Day-williams, Aaron

AU - Dedoussis, George

AU - Down, Thomas

AU - Du, Yuanping

AU - Van Duijn, Cornelia M.

AU - Dunham, Ian

AU - Edkins, Sarah

AU - Ekong, Rosemary

AU - Ellis, Peter

AU - Evans, David M.

AU - Farooqi, I. Sadaf

AU - Fitzpatrick, David R.

AU - Flicek, Paul

AU - Floyd, James

AU - Foley, A. Reghan

AU - Franklin, Christopher S.

AU - Futema, Marta

AU - Gallagher, Louise

AU - Gasparini, Paolo

AU - Gaunt, Tom R.

AU - Geihs, Matthias

AU - Geschwind, Daniel

AU - Greenwood, Celia

AU - Griffin, Heather

AU - Grozeva, Detelina

AU - Guo, Xiaosen

AU - Guo, Xueqin

AU - Gurling, Hugh

AU - Hart, Deborah

AU - Hendricks, Audrey E.

AU - Holmans, Peter

AU - Huang, Liren

AU - Hubbard, Tim

AU - Humphries, Steve E.

AU - Hurles, Matthew E.

AU - Hysi, Pirro

AU - Iotchkova, Valentina

AU - Isaacs, Aaron

AU - Jackson, David K.

AU - Jamshidi, Yalda

AU - Johnson, Jon

AU - Joyce, Chris

AU - Karczewski, Konrad J.

AU - Kaye, Jane

AU - Keane, Thomas

AU - Kemp, John P.

AU - Kennedy, Karen

AU - Kent, Alastair

AU - Keogh, Julia

AU - Khawaja, Farrah

AU - Kleber, Marcus E.

AU - Van Kogelenberg, Margriet

AU - Kolb-kokocinski, Anja

AU - Kooner, Jaspal S.

AU - Lachance, Genevieve

AU - Langenberg, Claudia

AU - Langford, Cordelia

AU - Lawson, Daniel

AU - Lee, Irene

AU - Van Leeuwen, Elisabeth M.

AU - Lek, Monkol

AU - Li, Rui

AU - Li, Yingrui

AU - Liang, Jieqin

AU - Lin, Hong

AU - Liu, Ryan

AU - Lönnqvist, Jouko

AU - Lopes, Luis R.

AU - Lopes, Margarida

AU - Luan, Jian'an

AU - Macarthur, Daniel G.

AU - Mangino, Massimo

AU - Marenne, Gaëlle

AU - März, Winfried

AU - Maslen, John

AU - Matchan, Angela

AU - Mathieson, Iain

AU - Mcguffin, Peter

AU - Mcintosh, Andrew M.

AU - Mckechanie, Andrew G.

AU - Mcquillin, Andrew

AU - Metrustry, Sarah

AU - Migone, Nicola

AU - Mitchison, Hannah M.

AU - Moayyeri, Alireza

AU - Morris, James

AU - Morris, Richard

AU - Muddyman, Dawn

AU - Muntoni, Francesco

AU - Nordestgaard, Børge

AU - Northstone, Kate

AU - O'donovan, Michael C.

AU - O'rahilly, Stephen

AU - Onoufriadis, Alexandros

AU - Oualkacha, Karim

AU - Owen, Michael J.

AU - Palotie, Aarno

AU - Panoutsopoulou, Kalliope

AU - Parker, Victoria

AU - Parr, Jeremy R.

AU - Paternoster, Lavinia

AU - Paunio, Tiina

AU - Payne, Felicity

AU - Payne, Stewart J.

AU - Perry, John R. B.

AU - Pietilainen, Olli

AU - Plagnol, Vincent

AU - Pollitt, Rebecca C.

AU - Povey, Sue

AU - Quail, Michael A.

AU - Quaye, Lydia

AU - Raymond, Lucy

AU - Rehnström, Karola

AU - Ridout, Cheryl K.

AU - Ring, Susan

AU - Ritchie, Graham R. S.

AU - Roberts, Nicola

AU - Robinson, Rachel L.

AU - Savage, David B.

AU - Scambler, Peter

AU - Schiffels, Stephan

AU - Schmidts, Miriam

AU - Schoenmakers, Nadia

AU - Scott, Richard H.

AU - Scott, Robert A.

AU - Semple, Robert K.

AU - Serra, Eva

AU - Sharp, Sally I.

AU - Shaw, Adam

AU - Shihab, Hashem A.

AU - Shin, So-youn

AU - Skuse, David

AU - Small, Kerrin S.

AU - Smee, Carol

AU - Smith, George Davey

AU - Southam, Lorraine

AU - Spasic-boskovic, Olivera

AU - Spector, Timothy D.

AU - St Clair, David

AU - St Pourcain, Beate

AU - Stalker, Jim

AU - Stevens, Elizabeth

AU - Sun, Jianping

AU - Surdulescu, Gabriela

AU - Suvisaari, Jaana

AU - Syrris, Petros

AU - Tachmazidou, Ioanna

AU - Taylor, Rohan

AU - Tian, Jing

AU - Tobin, Martin D.

AU - Toniolo, Daniela

AU - Traglia, Michela

AU - Tybjærg-Hansen, Anne

AU - Valdes, Ana M.

AU - Vandersteen, Anthony M.

AU - Varbo, Anette

AU - Vijayarangakannan, Parthiban

AU - Visscher, Peter M.

AU - Wain, Louise V.

AU - Walters, James T. R.

AU - Wang, Guangbiao

AU - Wang, Jun

AU - Wang, Yu

AU - Ward, Kirsten

AU - Wheeler, Eleanor

AU - Whincup, Peter

AU - Whyte, Tamieka

AU - Williams, Hywel J.

AU - Williamson, Kathleen A.

AU - Wilson, Crispian

AU - Wilson, Scott G.

AU - Wong, Kim

AU - Xu, Changjiang

AU - Yang, Jian

AU - Zaza, Gianluigi

AU - Zeggini, Eleftheria

AU - Zhang, Feng

AU - Zhang, Pingbo

AU - Zhang, Weihua

AU - Gambaro, Giovanni

AU - Richards, J. Brent

AU - Durbin, Richard

AU - Timpson, Nicholas J.

AU - Marchini, Jonathan

AU - Soranzo, Nicole

PY - 2015/9/14

Y1 - 2015/9/14

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms9111

DO - 10.1038/ncomms9111

M3 - Journal article

C2 - 26368830

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 8111

ER -

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

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