@article{van Leeuwen2015, abstract = {AbstractImputing 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 = {van Leeuwen, Elisabeth M. and van Leeuwen, Em and van Duijn, Cornelia M. and Zheng, Hou-Feng and Huang, Jie and Soranzo, N. and Al Turki, Saeed and Howie, Bryan and Amuzu, Antoinette and Anderson, Carl A. and Anney, Richard and Antony, Dinu and Artigas, María Soler and Soler Artigas, Maria and Ayub, Muhammad and Bala, Senduran and McCarthy, Shane and Barrett, Jeffrey C. and Barroso, Inês and Beales, Phil and Benn, Marianne and Turki, Saeed Al and Bentham, Jamie and Bhattacharya, Shoumo and Birney, Ewan and Blackwood, Douglas and Memari, Yasin and Bobrow, Martin and Bochukova, Elena and Bolton, Patrick F. and Bounds, Rebecca and Boustred, Chris and Min, Josine L. and Breen, Gerome and Calissano, Mattia and Carss, Keren and Walter, Klaudia and Chambers, John C. and Charlton, Ruth and Chatterjee, Krishna and Chen, Lu and Pablo Casas, Juan and Ciampi, Antonio and Cirak, Sebahattin and Clapham, Peter and Clement, Gail and Casas, Juan Pablo and Coates, Guy and Cocca, Massimiliano and Collier, David A. and Cosgrove, Catherine and Cox, Tony and Craddock, Nick and Crooks, Lucy and Curran, Sarah and Danecek, Petr and Curtis, David and Daly, Allan and Day, Ian N. M. and Van Duijn, C. M. and Day-Williams, Aaron and Dedoussis, George and Down, Thomas and Du, Yuanping and Malerba, Giovanni and Dunham, Ian and Edkins, Sarah and Ekong, Rosemary and Ellis, Peter and Evans, David M. and Farooqi, Is Sadaf and Fitzpatrick, David R. and Flicek, Paul and Trabetti, Elisabetta and Floyd, James and Foley, Ar Reghan and Franklin, Christopher S. and Sadaf Farooqi, I. and Futema, Marta and Gallagher, Louise and Gasparini, Paolo and Gaunt, Tom R. and Geihs, Matthias and Geschwind, Daniel and Greenwood, Celia and Griffin, Heather and Grozeva, Detelina and Guo, Xiaosen and Gurling, Hugh and Hart, Deborah and Hendricks, Audrey E. and Reghan Foley, A. and Holmans, Peter and Huang, Liren and Guo, Xueqin and Hubbard, Tim and Humphries, Steve E. and Hurles, Matthew E. and Hysi, Pirro and Iotchkova, Valentina and Isaacs, Aaron and Jackson, David K. and Jamshidi, Yalda and Johnson, Jon and Joyce, Chris and Karczewski, Konrad J. and Kaye, Jane and Keane, Thomas and Gambaro, Giovanni and Kemp, John P. and Jl, Min and Van Kogelenberg, M. and Kennedy, Karen and Walters, James T. R. and Kent, Alastair and Wang, Guangbiao and Keogh, Julia and Wang, Jun and Khawaja, Farrah and Wang, Yu and Kleber, Marcus E. and Ward, Kirsten and Durbin, Richard and Wheeler, Eleanor and Kolb-Kokocinski, Anja and Whincup, Peter and Kooner, Jaspal S. and Whyte, Tamieka and Van Leeuwen, E. M. and Lachance, Genevieve and Williams, Hywel J. and Langenberg, Claudia and Williamson, Kathleen A. and Richards, Jb Brent and Langford, Cordelia and Kogelenberg, Margriet Van and Wilson, Crispian and Lawson, Daniel and Wilson, Scott G. and Timpson, Nicholas J. and Lee, Irene and Wong, Kim and Xu, ChangJiang and Lek, Monkol and Yang, Jian and Li, Rui and Marchini, Jonathan and Zaza, Gianluigi and Li, Yingrui and Zeggini, Eleftheria and Zhang, Feng and Liang, Jieqin and Zhang, Pingbo Zhang & Weihua and Lin, Hong and Zhang, Weihua and Liu, Ryan and Lönnqvist, Jouko and Lopes, Luis R. and Lonnqvist, Jouko and Lopes, Margarida and Luan, Jian’an and MacArthur, Daniel G. and Mangino, Massimo and Marenne, Gaëlle and März, Winfried and Maslen, John and Matchan, Angela and März, Winfried and Mathieson, Iain and McGuffin, Peter and McIntosh, Andrew M. and McKechanie, Andrew G. and McQuillin, Andrew and Metrustry, Sarah and Migone, Nicola and Mitchison, Hannah M. and Moayyeri, Alireza and Mcguffin, P. and Morris, James and Morris, Richard and Muddyman, Dawn and Muntoni, Francesco and Mcintosh, Am and Nordestgaard, Børge G. and Northstone, Kate and Mckechanie, Ag and O'Donovan, Michael C. and O'Rahilly, Stephen and Onoufriadis, Alexandros and Oualkacha, Karim and Owen, Michael J. and Palotie, Aarno and Panoutsopoulou, Kalliope and Mcquillin, A. and Parker, Victoria and Parr, Jeremy R. and Paternoster, Lavinia and Paunio, Tiina and Payne, Felicity and Payne, Stewart J. and Perry, John R. B. and Pietilainen, Olli and Consortium, Uk K. and Plagnol, Vincent and Pollitt, Rebecca C. and Povey, Sue and Quail, Michael A. and Quaye, Lydia and Raymond, Lucy and Rehnström, Karola and Hf, Zheng and Ridout, Cheryl K. and Ring, Susan and Ritchie, Graham R. S. and Roberts, Nicola and Scott, R. H. and Robinson, Rachel L. and Scott, R. A. and Brent Richards, J. and Savage, David B. and Scambler, Peter and Schiffels, Stephan and Schmidts, Miriam and Schoenmakers, Nadia and Semple, Robert K. and Serra, Eva and Sharp, Sally I. and Shaw, Adam and Shihab, Hashem A. and Scott, Richard H. and Shin, So-Youn and Scott, Robert A. and Skuse, David and Small, Kerrin S. and Smee, Carol and Smith, George Davey and Southam, Lorraine and Spasic-Boskovic, Olivera and Soranzo, Nicole and Spector, Timothy D. and Stalker, Jim and Stevens, Elizabeth and Sun, Jianping and Uk10k, Consortium and Surdulescu, Gabriela and Suvisaari, Jaana and St Clair, David and Syrris, Petros and Davey Smith, George and Tachmazidou, Ioanna and St Pourcain, Beate and Taylor, Rohan and Tian, Jing and Tobin, Martin D. and Toniolo, Daniela and Traglia, Michela and Tybjaerg-Hansen, Anne and Valdes, Ana M. and Vandersteen, Anthony M. and Pourcain, Beate St and Varbo, Anette and Vijayarangakannan, Parthiban and Visscher, Peter M. and Wain, Louise V. and Jb, Richards and Soranzo, Jonathan Marchini & Nicole}, doi = {10.1038/ncomms9111}, journal = {Nature Communications}, month = {sep}, title = {Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel}, url = {https://www.nature.com/articles/ncomms9111.pdf}, volume = {6}, year = {2015} }