The UK10K project identifies rare variants in health and disease

• Verfasst von: Walter, Klaudia [VerfasserIn]
• Verfasst von: Kleber, Marcus E. [VerfasserIn]
• Verfasst von: März, Winfried [VerfasserIn]
• Titel: The UK10K project identifies rare variants in health and disease
• Verf.angabe: The UK10K Consortium: Writing group: 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. Hurles, Eleftheria Zeggini, Jeffrey C. Barrett, Vincent Plagnol, J. Brent Richards, Celia M.T. Greenwood, Nicholas J. Timpson, Richard Durbin and Nicole Soranzo; Production group: Senduran Bala, Peter Clapham, Guy Coates, Tony Cox, Allan Daly, Petr Danecek, Yuanping Du, Richard Durbin, 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, Shane McCarthy (co-chair), Dawn Muddyman, Michael A. Quail, Jim Stalker (co-chair), Jianping Sun, Jing Tian, Guangbiao Wang, Jun Wang, Yu Wang, Kim Wong and Pingbo Zhang; Cohorts group: Inês Barroso, Ewan Birney, Chris Boustred, Lu Chen, Gail Clement, Massimiliano Cocca, Petr Danecek, George Davey Smith, Ian N. M. Day, Aaron Day-Williams, Thomas Down, Ian Dunham, Richard Durbin, David M. Evans, Tom R. Gaunt, Matthias Geihs, Celia M.T. Greenwood, Deborah Hart, Audrey E. Hendricks, Bryan Howie, Jie Huang, Tim Hubbard, Pirro Hysi, Valentina Iotchkova, Yalda Jamshidi, Konrad J. Karczewski, John P. Kemp, Genevieve Lachance, Daniel Lawson, Monkol Lek, Margarida Lopes, Daniel G. MacArthur, Jonathan Marchini, Massimo Mangino, Iain Mathieson, Shane McCarthy, Yasin Memari, Sarah Metrustry, Josine L. Min, Alireza Moayyeri, Dawn Muddyman, Kate Northstone, Kalliope Panoutsopoulou, Lavinia Paternoster, John R.B. Perry, Lydia Quaye, J. Brent Richards (co-chair), Susan Ring, Graham R.S. Ritchie, Stephan Schiffels, Hashem A. Shihab, So-Youn Shin, Kerrin S. Small, María Soler Artigas, Nicole Soranzo (co-chair), Lorraine Southam, Timothy D. Spector, Beate St Pourcain, Gabriela Surdulescu, Ioanna Tachmazidou, Nicholas J. Timpson (co-chair), Martin D. Tobin, Ana M. Valdes, Peter M. Visscher, Louise V. Wain, Klaudia Walter, Kirsten Ward, Scott G. Wilson, Kim Wong, Jian Yang, Eleftheria Zeggini, Feng Zhang and Hou-Feng Zheng; Neurodevelopmental disorders group: Richard Anney, Muhammad Ayub, Jeffrey C. Barrett, Douglas Blackwood, Patrick F. Bolton, Gerome Breen, David A. Collier, Nick Craddock, Lucy Crooks, Sarah Curran, David Curtis, Richard Durbin, Louise Gallagher, Daniel Geschwind, Hugh Gurling, Peter Holmans, Irene Lee, Jouko Lönnqvist, Shane McCarthy, Peter McGuffin, Andrew M. McIntosh, Andrew G. McKechanie, Andrew McQuillin, James Morris, Dawn Muddyman, Michael C. O'Donovan, Michael J. Owen (co-chair), Aarno Palotie (co-chair), Jeremy R. Parr, Tiina Paunio, Olli Pietilainen, Karola Rehnström, Sally I. Sharp, David Skuse, David St Clair, Jaana Suvisaari, James T.R. Walters and Hywel J. Williams; Obesity group: Inês Barroso (co-chair), Elena Bochukova, Rebecca Bounds, Anna Dominiczak, Richard Durbin, I. Sadaf Farooqi (co-chair), Audrey E. Hendricks, Julia Keogh, Gaëlle Marenne, Shane McCarthy, Andrew Morris, Dawn Muddyman, Stephen O'Rahilly, David J. Porteous, Blair H. Smith, Ioanna Tachmazidou, Eleanor Wheeler and Eleftheria Zeggini; Rare disease group: Saeed Al Turki, Carl A. Anderson, Dinu Antony, Inês Barroso, Phil Beales, Jamie Bentham, Shoumo Bhattacharya, Mattia Calissano, Keren Carss, Krishna Chatterjee, Sebahattin Cirak, Catherine Cosgrove, Richard Durbin, David R. Fitzpatrick (co-chair), James Floyd, A. Reghan Foley, Christopher S. Franklin, Marta Futema, Detelina Grozeva, Steve E. Humphries, Matthew E. Hurles (co-chair), Shane McCarthy, Hannah M. Mitchison, Dawn Muddyman, Francesco Muntoni, Stephen O'Rahilly, Alexandros Onoufriadis, Victoria Parker, Felicity Payne, Vincent Plagnol, 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, Klaudia Walter, Kathleen A. Williamson, Crispian Wilson and Tamieka Whyte; Statistics group: Antonio Ciampi, Celia M.T. Greenwood (co-chair), Audrey E. Hendricks, Rui Li, Sarah Metrustry, Karim Oualkacha, Ioanna Tachmazidou, ChangJiang Xu and Eleftheria Zeggini (co-chair); Ethics group: Martin Bobrow, Patrick F. Bolton, Richard Durbin, David R. Fitzpatrick, Heather Griffin, Matthew E. Hurles (co-chair), Jane Kaye (co-chair), Karen Kennedy, Alastair Kent, Dawn Muddyman, Francesco Muntoni, F. Lucy Raymond, Robert K. Semple, Carol Smee, Timothy D. Spector and Nicholas J. Timpson; Incidental findings group: Ruth Charlton, Rosemary Ekong, Marta Futema, Steve E. Humphries, Farrah Khawaja, Luis R. Lopes, Nicola Migone, Stewart J. Payne, Vincent Plagnol (chair), Rebecca C. Pollitt, Sue Povey, Cheryl K. Ridout, Rachel L. Robinson, Richard H. Scott, Adam Shaw, Petros Syrris, Rohan Taylor and Anthony M. Vandersteen; Management committee: Jeffrey C. Barrett, Inês Barroso, George Davey Smith, Richard Durbin (chair), I. Sadaf Farooqi, David R. Fitzpatrick, Matthew E. Hurles, Jane Kaye, Karen Kennedy, Cordelia Langford, Shane McCarthy, Dawn Muddyman, Michael J. Owen, Aarno Palotie, J. Brent Richards, Nicole Soranzo, Timothy D. Spector, Jim Stalker, Nicholas J. Timpson and Eleftheria Zeggini; Lipid meta-analysis group: Antoinette Amuzu, Juan Pablo Casas, John C. Chambers, Massimiliano Cocca, George Dedoussis, Giovanni Gambaro, Paolo Gasparini, Tom R. Gaunt, Jie Huang, Valentina Iotchkova, Aaron Isaacs, Jon Johnson, Marcus E. Kleber, Jaspal S. Kooner, Claudia Langenberg, Jian’an Luan, Giovanni Malerba, Winfried März, Angela Matchan, Josine L. Min, Richard Morris, Børge G. Nordestgaard, Marianne Benn, Susan Ring, Robert A. Scott, Nicole Soranzo, Lorraine Southam, Nicholas J. Timpson, The UCLEB Consortium: Daniela Toniolo, Michela Traglia, Anne Tybjaerg-Hansen, Cornelia M. van Duijn, Elisabeth M. van Leeuwen, Anette Varbo, Peter Whincup, Gianluigi Zaza, Eleftheria Zeggini, Weihua Zhang
• E-Jahr: 2015
• Jahr: October 2015
• Umfang: 9 S.
• Fussnoten: Gesehen am 27.03.2018
• Titel Quelle: Enthalten in: Nature
• Ort Quelle: London [u.a.] : Nature Publ. Group, 1869
• Jahr Quelle: 2015
• Band/Heft Quelle: 526(2015), 7571, Seite 82-90
• ISSN Quelle: 1476-4687
• DOI: doi:10.1038/nature14962
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 157148387X

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.