학술논문
The UK10K project identifies rare variants in health and disease
Document Type
Academic Journal
Author
Walter, Klaudia; Min, Josine L.; Huang, Jie; Crooks, Lucy; Memari, Yasin; Perry, John R. B.; Xu, ChangJiang; Futema, Marta; Lawson, Daniel; Iotchkova, Valentina; Schiffels, Stephan; Hendricks, Audrey E.; Danecek, Petr; Li, Rui; Floyd, James; Wain, Louise V.; Humphries, Steve E.; Barrett, Jeffrey C.; Bala, Senduran; Clapham, Peter; Coates, Guy; Cox, Tony; Daly, Allan; Du, Yuanping; Edkins, Sarah; Ellis, Peter; Flicek, Paul; Guo, Xiaosen; Guo, Xueqin; Huang, Liren; Jackson, David K.; Joyce, Chris; Keane, Thomas; Kolb-Kokocinski, Anja; Langford, Cordelia; Li, Yingrui; Liang, Jieqin; Lin, Hong; Liu, Ryan; Maslen, John; McCarthy, Shane, (co-chair); Muddyman, Dawn; Quail, Michael A.; Stalker, Jim, (co-chair); Sun, Jianping; Tian, Jing; Wang, Guangbiao; Wang, Jun; Wang, Yu; Wong, Kim; Zhang, Pingbo; Birney, Ewan; Boustred, Chris; Chen, Lu; Clement, Gail; Cocca, Massimiliano; Smith, George Davey; Day, Ian N. M.; Day-Williams, Aaron; Down, Thomas; Dunham, Ian; Evans, David M.; Gaunt, Tom R.; Geihs, Matthias; Hart, Deborah; Howie, Bryan; Hubbard, Tim; Hysi, Pirro; Jamshidi, Yalda; Karczewski, Konrad J.; Kemp, John P.; Lachance, Genevieve; Lek, Monkol; Lopes, Margarida; MacArthur, Daniel G.; Marchini, Jonathan; Mangino, Massimo; Mathieson, Iain; Metrustry, Sarah; Moayyeri, Alireza; Northstone, Kate; Panoutsopoulou, Kalliope; Paternoster, Lavinia; Quaye, Lydia; Richards, Brent J., (co-chair); Ring, Susan; Ritchie, Graham R. S.; Shihab, Hashem A.; Shin, So-Youn; Small, Kerrin S.; Artigas, María Soler; Soranzo, Nicole, (co-chair); Southam, Lorraine; Spector, Timothy D.; St Pourcain, Beate; Surdulescu, Gabriela; Tachmazidou, Ioanna; Timpson, Nicholas J., (co-chair); Tobin, Martin D.; Valdes, Ana M.; Visscher, Peter M.; Ward, Kirsten; Wilson, Scott G.; Yang, Jian; Zhang, Feng; Zheng, Hou-Feng; Anney, Richard; Ayub, Muhammad; Blackwood, Douglas; Bolton, Patrick F.; Breen, Gerome; Collier, David A.; Craddock, Nick; Curran, Sarah; Curtis, David; Gallagher, Louise; Geschwind, Daniel; Gurling, Hugh; Holmans, Peter; Lee, Irene; Lönnqvist, Jouko; McGuffin, Peter; McIntosh, Andrew M.; McKechanie, Andrew G.; McQuillin, Andrew; Morris, James; OʼDonovan, Michael C.; Owen, Michael J., (co-chair); Palotie, Aarno, (co-chair); Parr, Jeremy R.; Paunio, Tiina; Pietilainen, Olli; Rehnström, Karola; Sharp, Sally I.; Skuse, David; St Clair, David; Suvisaari, Jaana; Walters, James T. R.; Williams, Hywel J.; Barroso, Inês, (co-chair); Bochukova, Elena; Bounds, Rebecca; Dominiczak, Anna; Farooqi, Sadaf I., (co-chair); Keogh, Julia; Marenne, Gaëlle; Morris, Andrew; OʼRahilly, Stephen; Porteous, David J.; Smith, Blair H.; Wheeler, Eleanor; Al Turki, Saeed; Anderson, Carl A.; Antony, Dinu; Beales, Phil; Bentham, Jamie; Bhattacharya, Shoumo; Calissano, Mattia; Carss, Keren; Chatterjee, Krishna; Cirak, Sebahattin; Cosgrove, Catherine; Fitzpatrick, David R., (co-chair); Foley, Reghan A.; Franklin, Christopher S.; Grozeva, Detelina; Hurles, Matthew E., (co-chair); Mitchison, Hannah M.; Muntoni, Francesco; Onoufriadis, Alexandros; Parker, Victoria; Payne, Felicity; Raymond, Lucy F.; Roberts, Nicola; Savage, David B.; Scambler, Peter; Schmidts, Miriam; Schoenmakers, Nadia; Semple, Robert K.; Serra, Eva; Spasic-Boskovic, Olivera; Stevens, Elizabeth; van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Williamson, Kathleen A.; Wilson, Crispian; Whyte, Tamieka; Ciampi, Antonio; Greenwood, Celia M. T., (co-chair); Oualkacha, Karim; Zeggini, Eleftheria, (co-chair); Bobrow, Martin; Griffin, Heather; Kaye, Jane, (co-chair); Kennedy, Karen; Kent, Alastair; Smee, Carol; Charlton, Ruth; Ekong, Rosemary; Khawaja, Farrah; Lopes, Luis R.; Migone, Nicola; Payne, Stewart J.; Plagnol, Vincent, (chair); Pollitt, Rebecca C.; Povey, Sue; Ridout, Cheryl K.; Robinson, Rachel L.; Scott, Richard H.; Shaw, Adam; Syrris, Petros; Taylor, Rohan; Vandersteen, Anthony M.; Durbin, Richard, (chair); Amuzu, Antoinette; Casas, Juan Pablo; Chambers, John C.; Dedoussis, George; Gambaro, Giovanni; Gasparini, Paolo; Isaacs, Aaron; Johnson, Jon; Kleber, Marcus E.; Kooner, Jaspal S.; Langenberg, Claudia; Luan, Jianʼan; Malerba, Giovanni; März, Winfried; Matchan, Angela; Morris, Richard; Nordestgaard, Børge G.; Benn, Marianne; Scott, Robert A.; Toniolo, Daniela; Traglia, Michela; Tybjaerg-Hansen, Anne; van Duijn, Cornelia M.; van Leeuwen, Elisabeth M.; Varbo, Anette; Whincup, Peter; Zaza, Gianluigi; Zhang, Weihua
Source
Nature. Oct 01, 2015 526(7571):82-90
Subject
Language
English
ISSN
0028-0836
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.