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. Hurles; Eleftheria 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

doi:10.1038/nature14962

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 journal › Article › peer-review

762 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 language	English
Pages (from-to)	82-89
Number of pages	8
Journal	Nature
Volume	526
Issue number	7571
DOIs	https://doi.org/10.1038/nature14962
State	Published - 1 Oct 2015
Externally published	Yes

Access to Document

10.1038/nature14962

Cite this

Walter, K., Min, J. L., Huang, J., Crooks, L., Memari, Y., McCarthy, S., Perry, J. R. B., Xu, C., Futema, M., Lawson, D., Iotchkova, V., Schiffels, S., Hendricks, A. E., Danecek, P., Li, R., Floyd, J., Wain, L. V., Barroso, I., Humphries, S. E., ... Zhang, W. (2015). The UK10K project identifies rare variants in health and disease. Nature, 526(7571), 82-89. https://doi.org/10.1038/nature14962

@article{92838b3864724b8abfd3e1c8c64bb2ac,

title = "The UK10K project identifies rare variants in health and disease",

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.",

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

year = "2015",

month = oct,

day = "1",

doi = "10.1038/nature14962",

language = "English",

volume = "526",

pages = "82--89",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7571",

}

Walter, K, Min, JL, Huang, J, Crooks, L, Memari, Y, McCarthy, S, Perry, JRB, Xu, C, Futema, M, Lawson, D, Iotchkova, V, Schiffels, S, Hendricks, AE, Danecek, P, Li, R, Floyd, J, Wain, LV, Barroso, I, Humphries, SE, Hurles, ME, Zeggini, E, Barrett, JC, Plagnol, V, Richards, JB, Greenwood, CMT, Timpson, NJ, Durbin, R, Bala, S, Clapham, P, Coates, G, Cox, T, Daly, A, Du, Y, Edkins, S, Ellis, P, Flicek, P, Guo, X, Guo, X, Huang, L, Jackson, DK, Joyce, C, Keane, T, Kolb-Kokocinski, A, Langford, C, Li, Y, Liang, J, Lin, H, Liu, R, Maslen, J, Muddyman, D, Quail, MA, Stalker, J, Sun, J, Tian, J, Wang, G, Wang, J, Wang, Y, Wong, K, Zhang, P, Birney, E, Boustred, C, Chen, L, Clement, G, Cocca, M, Smith, GD, Day, INM, Day-Williams, A, Down, T, Dunham, I, Evans, DM, Gaunt, TR, Geihs, M, Hart, D, Howie, B, Hubbard, T, Hysi, P, Jamshidi, Y, Karczewski, KJ, Kemp, JP, Lachance, G, Lek, M, Lopes, M, MacArthur, DG, Marchini, J, Mangino, M, Mathieson, I, Metrustry, S, Moayyeri, A, Northstone, K, Panoutsopoulou, K, Paternoster, L, Quaye, L, Ring, S, Ritchie, GRS, Shihab, HA, Shin, SY, Small, KS, Artigas, MS, Soranzo, N, Southam, L, Spector, TD, St Pourcain, B, Surdulescu, G, Tachmazidou, I, Tobin, MD, Valdes, AM, Visscher, PM, Ward, K, Wilson, SG, Yang, J, Zhang, F, Zheng, HF, Anney, R, Ayub, M, Blackwood, D, Bolton, PF, Breen, G, Collier, DA, Craddock, N, Curran, S, Curtis, D, Gallagher, L, Geschwind, D, Gurling, H, Holmans, P, Lee, I, Lönnqvist, J, McGuffin, P, McIntosh, AM, McKechanie, AG, McQuillin, A, Morris, J, O'Donovan, MC, Owen, MJ, Palotie, A, Parr, JR, Paunio, T, Pietilainen, O, Rehnström, K, Sharp, SI, Skuse, D, St Clair, D, Suvisaari, J, Walters, JTR, Williams, HJ, Bochukova, E, Bounds, R, Dominiczak, A, Farooqi, IS, Keogh, J, Marenne, G, Morris, A, O'Rahilly, S, Porteous, DJ, Smith, BH, Wheeler, E, Al Turki, S, Anderson, CA, Antony, D, Beales, P, Bentham, J, Bhattacharya, S, Calissano, M, Carss, K, Chatterjee, K, Cirak, S, Cosgrove, C, Fitzpatrick, DR, Foley, AR, Franklin, CS, Grozeva, D, Mitchison, HM, Muntoni, F, Onoufriadis, A, Parker, V, Payne, F, Raymond, FL, Roberts, N, Savage, DB, Scambler, P, Schmidts, M, Schoenmakers, N, Semple, RK, Serra, E, Spasic-Boskovic, O, Stevens, E, Van Kogelenberg, M, Vijayarangakannan, P, Williamson, KA, Wilson, C, Whyte, T, Ciampi, A, Oualkacha, K, Bobrow, M, Griffin, H, Kaye, J, Kennedy, K, Kent, A, Smee, C, Charlton, R, Ekong, R, Khawaja, F, Lopes, LR, Migone, N, Payne, SJ, Pollitt, RC, Povey, S, Ridout, CK, Robinson, RL, Scott, RH, Shaw, A, Syrris, P, Taylor, R, Vandersteen, AM, Amuzu, A, Casas, JP, Chambers, JC, Dedoussis, G, Gambaro, G, Gasparini, P, Isaacs, A, Johnson, J, Kleber, ME, Kooner, JS, Langenberg, C, Luan, J, Malerba, G, März, W, Matchan, A, Morris, R, Nordestgaard, BG, Benn, M, Scott, RA, Toniolo, D, Traglia, M, Tybjaerg-Hansen, A, Van Duijn, CM, Van Leeuwen, EM, Varbo, A, Whincup, P, Zaza, G & Zhang, W 2015, 'The UK10K project identifies rare variants in health and disease', Nature, vol. 526, no. 7571, pp. 82-89. https://doi.org/10.1038/nature14962

TY - JOUR

T1 - The UK10K project identifies rare variants in health and disease

AU - Walter, Klaudia

AU - Min, Josine L.

AU - Huang, Jie

AU - Crooks, Lucy

AU - Memari, Yasin

AU - McCarthy, Shane

AU - Perry, John R.B.

AU - Xu, Changjiang

AU - Futema, Marta

AU - Lawson, Daniel

AU - Iotchkova, Valentina

AU - Schiffels, Stephan

AU - Hendricks, Audrey E.

AU - Danecek, Petr

AU - Li, Rui

AU - Floyd, James

AU - Wain, Louise V.

AU - Barroso, Inês

AU - Humphries, Steve E.

AU - Hurles, Matthew E.

AU - Zeggini, Eleftheria

AU - Barrett, Jeffrey C.

AU - Plagnol, Vincent

AU - Richards, J. Brent

AU - Greenwood, Celia M.T.

AU - Timpson, Nicholas J.

AU - Durbin, Richard

AU - Bala, Senduran

AU - Clapham, Peter

AU - Coates, Guy

AU - Cox, Tony

AU - Daly, Allan

AU - Du, Yuanping

AU - Edkins, Sarah

AU - Ellis, Peter

AU - Flicek, Paul

AU - Guo, Xiaosen

AU - Guo, Xueqin

AU - Huang, Liren

AU - Jackson, David K.

AU - Joyce, Chris

AU - Keane, Thomas

AU - Kolb-Kokocinski, Anja

AU - Langford, Cordelia

AU - Li, Yingrui

AU - Liang, Jieqin

AU - Lin, Hong

AU - Liu, Ryan

AU - Maslen, John

AU - Muddyman, Dawn

AU - Quail, Michael A.

AU - Stalker, Jim

AU - Sun, Jianping

AU - Tian, Jing

AU - Wang, Guangbiao

AU - Wang, Jun

AU - Wang, Yu

AU - Wong, Kim

AU - Zhang, Pingbo

AU - Birney, Ewan

AU - Boustred, Chris

AU - Chen, Lu

AU - Clement, Gail

AU - Cocca, Massimiliano

AU - Smith, George Davey

AU - Day, Ian N.M.

AU - Day-Williams, Aaron

AU - Down, Thomas

AU - Dunham, Ian

AU - Evans, David M.

AU - Gaunt, Tom R.

AU - Geihs, Matthias

AU - Hart, Deborah

AU - Howie, Bryan

AU - Hubbard, Tim

AU - Hysi, Pirro

AU - Jamshidi, Yalda

AU - Karczewski, Konrad J.

AU - Kemp, John P.

AU - Lachance, Genevieve

AU - Lek, Monkol

AU - Lopes, Margarida

AU - MacArthur, Daniel G.

AU - Marchini, Jonathan

AU - Mangino, Massimo

AU - Mathieson, Iain

AU - Metrustry, Sarah

AU - Moayyeri, Alireza

AU - Northstone, Kate

AU - Panoutsopoulou, Kalliope

AU - Paternoster, Lavinia

AU - Quaye, Lydia

AU - Ring, Susan

AU - Ritchie, Graham R.S.

AU - Shihab, Hashem A.

AU - Shin, So Youn

AU - Small, Kerrin S.

AU - Artigas, María Soler

AU - Soranzo, Nicole

AU - Southam, Lorraine

AU - Spector, Timothy D.

AU - St Pourcain, Beate

AU - Surdulescu, Gabriela

AU - Tachmazidou, Ioanna

AU - Tobin, Martin D.

AU - Valdes, Ana M.

AU - Visscher, Peter M.

AU - Ward, Kirsten

AU - Wilson, Scott G.

AU - Yang, Jian

AU - Zhang, Feng

AU - Zheng, Hou Feng

AU - Anney, Richard

AU - Ayub, Muhammad

AU - Blackwood, Douglas

AU - Bolton, Patrick F.

AU - Breen, Gerome

AU - Collier, David A.

AU - Craddock, Nick

AU - Curran, Sarah

AU - Curtis, David

AU - Gallagher, Louise

AU - Geschwind, Daniel

AU - Gurling, Hugh

AU - Holmans, Peter

AU - Lee, Irene

AU - Lönnqvist, Jouko

AU - McGuffin, Peter

AU - McIntosh, Andrew M.

AU - McKechanie, Andrew G.

AU - McQuillin, Andrew

AU - Morris, James

AU - O'Donovan, Michael C.

AU - Owen, Michael J.

AU - Palotie, Aarno

AU - Parr, Jeremy R.

AU - Paunio, Tiina

AU - Pietilainen, Olli

AU - Rehnström, Karola

AU - Sharp, Sally I.

AU - Skuse, David

AU - St Clair, David

AU - Suvisaari, Jaana

AU - Walters, James T.R.

AU - Williams, Hywel J.

AU - Bochukova, Elena

AU - Bounds, Rebecca

AU - Dominiczak, Anna

AU - Farooqi, I. Sadaf

AU - Keogh, Julia

AU - Marenne, Gaëlle

AU - Morris, Andrew

AU - O'Rahilly, Stephen

AU - Porteous, David J.

AU - Smith, Blair H.

AU - Wheeler, Eleanor

AU - Al Turki, Saeed

AU - Anderson, Carl A.

AU - Antony, Dinu

AU - Beales, Phil

AU - Bentham, Jamie

AU - Bhattacharya, Shoumo

AU - Calissano, Mattia

AU - Carss, Keren

AU - Chatterjee, Krishna

AU - Cirak, Sebahattin

AU - Cosgrove, Catherine

AU - Fitzpatrick, David R.

AU - Foley, A. Reghan

AU - Franklin, Christopher S.

AU - Grozeva, Detelina

AU - Mitchison, Hannah M.

AU - Muntoni, Francesco

AU - Onoufriadis, Alexandros

AU - Parker, Victoria

AU - Payne, Felicity

AU - Raymond, F. Lucy

AU - Roberts, Nicola

AU - Savage, David B.

AU - Scambler, Peter

AU - Schmidts, Miriam

AU - Schoenmakers, Nadia

AU - Semple, Robert K.

AU - Serra, Eva

AU - Spasic-Boskovic, Olivera

AU - Stevens, Elizabeth

AU - Van Kogelenberg, Margriet

AU - Vijayarangakannan, Parthiban

AU - Williamson, Kathleen A.

AU - Wilson, Crispian

AU - Whyte, Tamieka

AU - Ciampi, Antonio

AU - Oualkacha, Karim

AU - Bobrow, Martin

AU - Griffin, Heather

AU - Kaye, Jane

AU - Kennedy, Karen

AU - Kent, Alastair

AU - Smee, Carol

AU - Charlton, Ruth

AU - Ekong, Rosemary

AU - Khawaja, Farrah

AU - Lopes, Luis R.

AU - Migone, Nicola

AU - Payne, Stewart J.

AU - Pollitt, Rebecca C.

AU - Povey, Sue

AU - Ridout, Cheryl K.

AU - Robinson, Rachel L.

AU - Scott, Richard H.

AU - Shaw, Adam

AU - Syrris, Petros

AU - Taylor, Rohan

AU - Vandersteen, Anthony M.

AU - Amuzu, Antoinette

AU - Casas, Juan Pablo

AU - Chambers, John C.

AU - Dedoussis, George

AU - Gambaro, Giovanni

AU - Gasparini, Paolo

AU - Isaacs, Aaron

AU - Johnson, Jon

AU - Kleber, Marcus E.

AU - Kooner, Jaspal S.

AU - Langenberg, Claudia

AU - Luan, Jian'an

AU - Malerba, Giovanni

AU - März, Winfried

AU - Matchan, Angela

AU - Morris, Richard

AU - Nordestgaard, Børge G.

AU - Benn, Marianne

AU - Scott, Robert A.

AU - Toniolo, Daniela

AU - Traglia, Michela

AU - Tybjaerg-Hansen, Anne

AU - Van Duijn, Cornelia M.

AU - Van Leeuwen, Elisabeth M.

AU - Varbo, Anette

AU - Whincup, Peter

AU - Zaza, Gianluigi

AU - Zhang, Weihua

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84943182742&partnerID=8YFLogxK

U2 - 10.1038/nature14962

DO - 10.1038/nature14962

M3 - Article

C2 - 26367797

AN - SCOPUS:84943182742

SN - 0028-0836

VL - 526

SP - 82

EP - 89

JO - Nature

JF - Nature

IS - 7571

ER -

The UK10K project identifies rare variants in health and disease

Abstract

Access to Document

Fingerprint

Cite this