The UK10K project identifies rare variants in health and disease

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

Research output: Contribution to journalArticlepeer-review

636 Scopus citations

Abstract

The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.

Original languageEnglish
Pages (from-to)82-89
Number of pages8
JournalNature
Volume526
Issue number7571
DOIs
StatePublished - 1 Oct 2015
Externally publishedYes

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