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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Jie Huang, Bryan Howie, Shane McCarthy, Yasin Memari, Klaudia Walter, Josine L. Min, Petr Danecek, Giovanni Malerba, Elisabetta Trabetti, Hou-Feng Zheng, UK10K Consortium, 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 G. 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 Tybjaerg-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

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. More... »

PAGES

8111

Journal

TITLE

Nature Communications

ISSUE

1

VOLUME

6

Author Affiliations

  • Wellcome Sanger Institute
  • Adaptive Biotechnologies (United States)
  • University of Bristol
  • University of Verona
  • McGill University
  • King Abdulaziz Medical City
  • London School of Hygiene & Tropical Medicine
  • St. James's Hospital
  • University College London
  • University of Leicester
  • Queen's University
  • University of Cambridge
  • University of Copenhagen
  • European Bioinformatics Institute
  • University of Edinburgh
  • King's College London
  • National Health Service
  • Imperial College London
  • St James's University Hospital
  • University Hospital Cologne
  • University of Trieste
  • Eli Lilly (United Kingdom)
  • Cardiff University
  • Sheffield Children's NHS Foundation Trust
  • Sussex Partnership NHS Foundation Trust
  • Biogen (United States)
  • Harokopio University
  • Beijing Genomics Institute
  • Erasmus University Medical Center
  • University of Queensland
  • University of California Los Angeles
  • University of Oxford
  • University of Colorado Denver
  • Broad Institute
  • National Cancer Research Institute
  • Genetic Alliance UK (United Kingdom)
  • St George's, University of London
  • MRC Epidemiology Unit
  • Massachusetts General Hospital
  • National Institute for Health and Welfare
  • University of Lisbon
  • Illumina (United Kingdom)
  • National Institute for Health Research
  • Heidelberg University
  • Harvard University
  • University of Turin
  • University of Quebec at Montreal
  • University of Helsinki
  • Newcastle University
  • Northwick Park Hospital
  • Guy's Hospital
  • Radboud Institute for Molecular Life Sciences
  • Great Ormond Street Hospital
  • Guy's and St Thomas' NHS Foundation Trust
  • Wellcome Centre for Human Genetics
  • University of Aberdeen
  • Glenfield Hospital
  • San Raffaele Hospital
  • University of Hong Kong
  • Sir Charles Gairdner Hospital
  • Catholic University of the Sacred Heart
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms9111

    DOI

    http://dx.doi.org/10.1038/ncomms9111

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1044833567

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26368830


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