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

• DOI: 10.1038/ncomms9111
• Publication Date: 2015-09-14T14:58:08Z
• Authors: 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 D...; 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. Fr...; 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 Koge...; Anja Kolb-Kokocinski; Jaspal S. Kooner; Genevieve Lachance; Claudia Langenberg; Cordelia Langford; Daniel Lawson; Irene Lee; Elisabeth M. van ...; 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 G. Nordestg...; Kate Northstone; Michael C. O'Donovan; Stephen O'Rahilly; Alexandros Onoufr...; Karim Oualkacha; Michael J. Owen; Aarno Palotie; Kalliope Panoutso...; 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-Bo...; 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 Tybjaerg-Hansen; Ana M. Valdes; Anthony M. Vander...; Anette Varbo; Parthiban Vijayar...; 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. Willi...; 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
• Keywords: Imputation (statistics); 1000 Genomes Project; Minor allele frequency; Genome-wide Association Study; SNP

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 data set 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down 0.1% minor allele frequency in British population. Here we demonstrate value this resource improving imputation accuracy rare and low-frequency variants both UK an Italian We show that large increases can be achieved re-phasing WGS after initial genotype calling. also present method combining improve variant coverage downstream accuracy, which illustrate integrating 7,562 haplotypes with 2,184 1000 Genomes Project. Finally, introduce novel approximation maintains speed without sacrificing variants.