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

2015; Nature Portfolio; Volume: 6; Issue: 1 Linguagem: Inglês

10.1038/ncomms9111

2041-1723

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 G. Bochukova, Patrick Bolton, Rebecca Bounds, Chris Boustred, Gerome Breen, Mattia Calissano, Keren Carss, Juan P. Casas, John C. Chambers, Ruth Charlton, Krishna Chatterjee, Lu Chen, Antonio Ciampi, Sebahattin Çırak, Peter Clapham, Gail Clement, Guy Coates, Massimiliano Cocca, David Collier, Catherine Cosgrove, Tony Cox, Nick Craddock, Lucy Crooks, Sarah Curran, David Curtis, Allan Daly, Ian N.M. Day, Aaron G. Day‐Williams, George Dedoussis, Thomas A. Down, Yuanping Du, Cornelia M. van Duijn, Ian Dunham, Sarah Edkins, Rosemary Ekong, Peter Ellis, David M. Evans, I. Sadaf Farooqi, David Fitzpatrick, Paul Flicek, James Floyd, A. Reghan Foley, Christopher S. Franklin, Marta Futema, Louise Gallagher, Paolo Gasparini, Tom R. Gaunt, Matthias Geihs, Daniel H. Geschwind, Celia M.T. Greenwood, Heather Griffin, Detelina Grozeva, Xiaosen Guo, Xueqin Guo, Hugh Gurling, Deborah Hart, Audrey E. Hendricks, Peter Holmans, Jie Huang, Tim Hubbard, Steve E. Humphries, Matthew E. Hurles, Pirro G. Hysi, Valentina Iotchkova, Aaron Isaacs, David K. Jackson, Yalda Jamshidi, Jon Johnson, Christopher Joyce, Konrad J. Karczewski, Jane Kaye, Thomas Keane, John P. Kemp, Karen Kennedy, Alastair Kent, Julia M. Keogh, Farrah Khawaja, Marcus E. Kleber, Margriet van Kogelenberg, Anja Kolb-Kokocinski, Jaspal S. Kooner, Geneviève Lachance, Claudia Langenberg, Cordelia Langford, Daniel J. Lawson, Irene Lee, Jin‐Moo Lee, Monkol Lek, Rui Li, Rui Li, Jieqin Liang, Hong Lin, Ryan Liu, Jouko Lönnqvist, Luís 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 G. Nordestgaard, Kate Northstone, Michael O’Donovan, Stephen O’Rahilly, Alexandros Onoufriadis, Karim Oualkacha, Michael J. Owen, Aarno Palotie, Kalliope Panoutsopoulou, Victoria Parker, Jeremy Parr, Lavinia Paternoster, Tiina Paunio, Felicity Payne, Stewart J. Payne, John R. B. Perry, Olli Pietiläinen, Vincent Plagnol, Rebecca C. Pollitt, Sue Povey, Michael A. Quail, Lydia Quaye, Lucy Raymond, Karola Rehnström, Cheryl K. Ridout, Susan M. 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 Spasić-Bošković, Timothy D. Spector, David St Clair, Beaté 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 Walters, Guangbiao Wang, Jun Wang, Yu Wang, Kirsten Ward, Eleanor Wheeler, Peter H. Whincup, Tamieka Whyte, Hywel 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,

Genetic and phenotypic traits in livestock

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.