The UK10K project identifies rare variants in health and disease

K. Walter, J.L. Min, J. Huang, L. Crooks, Y. Memari, S. Mccarthy, J.R.B. Perry, C. Xu, M. Futema, D. Lawson, V. Iotchkova, S. Schiffels, A.E. Hendricks, P. Danecek, R. Li, J. Floyd, L.V. Wain, I. Barroso, S.E. Humphries, M.E. Hurles & 221 others E. Zeggini, J.C. Barrett, V. Plagnol, J.B. Richards, C.M.T. Greenwood, N.J. Timpson, R. Durbin, S. Bala, P. Clapham, G. Coates, T. Cox, A. Daly, Y. Du, S. Edkins, P. Ellis, P. Flicek, X. Guo, L. Huang, D.K. Jackson, C. Joyce, T. Keane, A. Kolb-Kokocinski, C. Langford, Y. Li, J. Liang, H. Lin, R. Liu, J. Maslen, D. Muddyman, M.A. Quail, J. Stalker, J. Sun, J. Tian, G. Wang, J. Wang, Y. Wang, K. Wong, P. Zhang, E. Birney, C. Boustred, L. Chen, G. Clement, M. Cocca, G.D. Smith, I.N.M. Day, A. Day-Williams, T. Down, I. Dunham, D.M. Evans, T.R. Gaunt, M. Geihs, D. Hart, B. Howie, T. Hubbard, P. Hysi, Y. Jamshidi, K.J. Karczewski, J.P. Kemp, G. Lachance, M. Lek, M. Lopes, D.G. Macarthur, J. Marchini, M. Mangino, I. Mathieson, S. Metrustry, A. Moayyeri, K. Northstone, K. Panoutsopoulou, L. Paternoster, L. Quaye, S. Ring, G.R.S. Ritchie, H.A. Shihab, S.-Y. Shin, K.S. Small, M.S. Artigas, N. Soranzo, L. Southam, T.D. Spector, B. St Pourcain, G. Surdulescu, I. Tachmazidou, M.D. Tobin, A.M. Valdes, P.M. Visscher, K. Ward, Scott Wilson, J. Yang, F. Zhang, H.-F. Zheng, R. Anney, M. Ayub, D. Blackwood, P.F. Bolton, G. Breen, D.A. Collier, N. Craddock, S. Curran, D. Curtis, L. Gallagher, D. Geschwind, H. Gurling, P. Holmans, I. Lee, J. Lönnqvist, P. Mcguffin, A.M. Mcintosh, A.G. Mckechanie, A. Mcquillin, J. Morris, M.C. O'Donovan, M.J. Owen, A. Palotie, J.R. Parr, T. Paunio, O. Pietilainen, K. Rehnström, S.I. Sharp, D. Skuse, D. St Clair, J. Suvisaari, J.T.R. Walters, H.J. Williams, E. Bochukova, R. Bounds, A. Dominiczak, I.S. Farooqi, J. Keogh, G. Marenne, A. Morris, S. O'Rahilly, D.J. Porteous, B.H. Smith, E. Wheeler, S. Al Turki, C.A. Anderson, D. Antony, P. Beales, J. Bentham, S. Bhattacharya, M. Calissano, K. Carss, K. Chatterjee, S. Cirak, C. Cosgrove, D.R. Fitzpatrick, A.R. Foley, C.S. Franklin, D. Grozeva, H.M. Mitchison, F. Muntoni, A. Onoufriadis, V. Parker, F. Payne, F.L. Raymond, N. Roberts, D.B. Savage, P. Scambler, M. Schmidts, N. Schoenmakers, R.K. Semple, E. Serra, O. Spasic-Boskovic, E. Stevens, M. Van Kogelenberg, P. Vijayarangakannan, K.A. Williamson, C. Wilson, T. Whyte, A. Ciampi, K. Oualkacha, M. Bobrow, H. Griffin, J. Kaye, K. Kennedy, A. Kent, C. Smee, R. Charlton, R. Ekong, F. Khawaja, L.R. Lopes, N. Migone, S.J. Payne, R.C. Pollitt, S. Povey, C.K. Ridout, R.L. Robinson, R.H. Scott, A. Shaw, P. Syrris, R. Taylor, A.M. Vandersteen, A. Amuzu, J.P. Casas, J.C. Chambers, G. Dedoussis, G. Gambaro, P. Gasparini, A. Isaacs, J. Johnson, M.E. Kleber, J.S. Kooner, C. Langenberg, J. Luan, G. Malerba, W. März, A. Matchan, R. Morris, B.G. Nordestgaard, M. Benn, R.A. Scott, D. Toniolo, M. Traglia, A. Tybjaerg-Hansen, C.M. Van Duijn, E.M. Van Leeuwen, A. Varbo, P. Whincup, G. Zaza, W. Zhang

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Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. 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
JournalNature
Volume526
Issue number7571
DOIs
Publication statusPublished - 2015

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Walter, K., Min, J. L., Huang, J., Crooks, L., Memari, Y., Mccarthy, S., ... Zhang, W. (2015). The UK10K project identifies rare variants in health and disease. Nature, 526(7571), 82-89. https://doi.org/10.1038/nature14962
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. ; Hurles, M.E. ; Zeggini, E. ; Barrett, J.C. ; Plagnol, V. ; Richards, J.B. ; Greenwood, C.M.T. ; Timpson, N.J. ; Durbin, R. ; Bala, S. ; Clapham, P. ; Coates, G. ; Cox, T. ; Daly, A. ; Du, Y. ; Edkins, S. ; Ellis, P. ; Flicek, P. ; Guo, X. ; Huang, L. ; Jackson, D.K. ; Joyce, C. ; Keane, T. ; Kolb-Kokocinski, A. ; Langford, C. ; Li, Y. ; Liang, J. ; Lin, H. ; Liu, R. ; Maslen, J. ; Muddyman, D. ; Quail, M.A. ; 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, G.D. ; Day, I.N.M. ; Day-Williams, A. ; Down, T. ; Dunham, I. ; Evans, D.M. ; Gaunt, T.R. ; Geihs, M. ; Hart, D. ; Howie, B. ; Hubbard, T. ; Hysi, P. ; Jamshidi, Y. ; Karczewski, K.J. ; Kemp, J.P. ; Lachance, G. ; Lek, M. ; Lopes, M. ; Macarthur, D.G. ; Marchini, J. ; Mangino, M. ; Mathieson, I. ; Metrustry, S. ; Moayyeri, A. ; Northstone, K. ; Panoutsopoulou, K. ; Paternoster, L. ; Quaye, L. ; Ring, S. ; Ritchie, G.R.S. ; Shihab, H.A. ; Shin, S.-Y. ; Small, K.S. ; Artigas, M.S. ; Soranzo, N. ; Southam, L. ; Spector, T.D. ; St Pourcain, B. ; Surdulescu, G. ; Tachmazidou, I. ; Tobin, M.D. ; Valdes, A.M. ; Visscher, P.M. ; Ward, K. ; Wilson, Scott ; Yang, J. ; Zhang, F. ; Zheng, H.-F. ; Anney, R. ; Ayub, M. ; Blackwood, D. ; Bolton, P.F. ; Breen, G. ; Collier, D.A. ; Craddock, N. ; Curran, S. ; Curtis, D. ; Gallagher, L. ; Geschwind, D. ; Gurling, H. ; Holmans, P. ; Lee, I. ; Lönnqvist, J. ; Mcguffin, P. ; Mcintosh, A.M. ; Mckechanie, A.G. ; Mcquillin, A. ; Morris, J. ; O'Donovan, M.C. ; Owen, M.J. ; Palotie, A. ; Parr, J.R. ; Paunio, T. ; Pietilainen, O. ; Rehnström, K. ; Sharp, S.I. ; Skuse, D. ; St Clair, D. ; Suvisaari, J. ; Walters, J.T.R. ; Williams, H.J. ; Bochukova, E. ; Bounds, R. ; Dominiczak, A. ; Farooqi, I.S. ; Keogh, J. ; Marenne, G. ; Morris, A. ; O'Rahilly, S. ; Porteous, D.J. ; Smith, B.H. ; Wheeler, E. ; Al Turki, S. ; Anderson, C.A. ; Antony, D. ; Beales, P. ; Bentham, J. ; Bhattacharya, S. ; Calissano, M. ; Carss, K. ; Chatterjee, K. ; Cirak, S. ; Cosgrove, C. ; Fitzpatrick, D.R. ; Foley, A.R. ; Franklin, C.S. ; Grozeva, D. ; Mitchison, H.M. ; Muntoni, F. ; Onoufriadis, A. ; Parker, V. ; Payne, F. ; Raymond, F.L. ; Roberts, N. ; Savage, D.B. ; Scambler, P. ; Schmidts, M. ; Schoenmakers, N. ; Semple, R.K. ; Serra, E. ; Spasic-Boskovic, O. ; Stevens, E. ; Van Kogelenberg, M. ; Vijayarangakannan, P. ; Williamson, K.A. ; 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, L.R. ; Migone, N. ; Payne, S.J. ; Pollitt, R.C. ; Povey, S. ; Ridout, C.K. ; Robinson, R.L. ; Scott, R.H. ; Shaw, A. ; Syrris, P. ; Taylor, R. ; Vandersteen, A.M. ; Amuzu, A. ; Casas, J.P. ; Chambers, J.C. ; Dedoussis, G. ; Gambaro, G. ; Gasparini, P. ; Isaacs, A. ; Johnson, J. ; Kleber, M.E. ; Kooner, J.S. ; Langenberg, C. ; Luan, J. ; Malerba, G. ; März, W. ; Matchan, A. ; Morris, R. ; Nordestgaard, B.G. ; Benn, M. ; Scott, R.A. ; Toniolo, D. ; Traglia, M. ; Tybjaerg-Hansen, A. ; Van Duijn, C.M. ; Van Leeuwen, E.M. ; Varbo, A. ; Whincup, P. ; Zaza, G. ; Zhang, W. / The UK10K project identifies rare variants in health and disease. In: Nature. 2015 ; Vol. 526, No. 7571. pp. 82-89.
@article{d3ed4681c35c4abd8fb7b643319fa4ab,
title = "The UK10K project identifies rare variants in health and disease",
abstract = "{\circledC} 2015 Macmillan Publishers Limited. All rights reserved. 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 = "K. Walter and J.L. Min and J. Huang and L. Crooks and Y. Memari and S. Mccarthy and J.R.B. Perry and C. Xu and M. Futema and D. Lawson and V. Iotchkova and S. Schiffels and A.E. Hendricks and P. Danecek and R. Li and J. Floyd and L.V. Wain and I. Barroso and S.E. Humphries and M.E. Hurles and E. Zeggini and J.C. Barrett and V. Plagnol and J.B. Richards and C.M.T. Greenwood and N.J. Timpson and R. Durbin and S. Bala and P. Clapham and G. Coates and T. Cox and A. Daly and Y. Du and S. Edkins and P. Ellis and P. Flicek and X. Guo and L. Huang and D.K. Jackson and C. Joyce and T. Keane and A. Kolb-Kokocinski and C. Langford and Y. Li and J. Liang and H. Lin and R. Liu and J. Maslen and D. Muddyman and M.A. Quail and J. Stalker and J. Sun and J. Tian and G. Wang and J. Wang and Y. Wang and K. Wong and P. Zhang and E. Birney and C. Boustred and L. Chen and G. Clement and M. Cocca and G.D. Smith and I.N.M. Day and A. Day-Williams and T. Down and I. Dunham and D.M. Evans and T.R. Gaunt and M. Geihs and D. Hart and B. Howie and T. Hubbard and P. Hysi and Y. Jamshidi and K.J. Karczewski and J.P. Kemp and G. Lachance and M. Lek and M. Lopes and D.G. Macarthur and J. Marchini and M. Mangino and I. Mathieson and S. Metrustry and A. Moayyeri and K. Northstone and K. Panoutsopoulou and L. Paternoster and L. Quaye and S. Ring and G.R.S. Ritchie and H.A. Shihab and S.-Y. Shin and K.S. Small and M.S. Artigas and N. Soranzo and L. Southam and T.D. Spector and {St Pourcain}, B. and G. Surdulescu and I. Tachmazidou and M.D. Tobin and A.M. Valdes and P.M. Visscher and K. Ward and Scott Wilson and J. Yang and F. Zhang and H.-F. Zheng and R. Anney and M. Ayub and D. Blackwood and P.F. Bolton and G. Breen and D.A. Collier and N. Craddock and S. Curran and D. Curtis and L. Gallagher and D. Geschwind and H. Gurling and P. Holmans and I. Lee and J. L{\"o}nnqvist and P. Mcguffin and A.M. Mcintosh and A.G. Mckechanie and A. Mcquillin and J. Morris and M.C. O'Donovan and M.J. Owen and A. Palotie and J.R. Parr and T. Paunio and O. Pietilainen and K. Rehnstr{\"o}m and S.I. Sharp and D. Skuse and {St Clair}, D. and J. Suvisaari and J.T.R. Walters and H.J. Williams and E. Bochukova and R. Bounds and A. Dominiczak and I.S. Farooqi and J. Keogh and G. Marenne and A. Morris and S. O'Rahilly and D.J. Porteous and B.H. Smith and E. Wheeler and {Al Turki}, S. and C.A. Anderson and D. Antony and P. Beales and J. Bentham and S. Bhattacharya and M. Calissano and K. Carss and K. Chatterjee and S. Cirak and C. Cosgrove and D.R. Fitzpatrick and A.R. Foley and C.S. Franklin and D. Grozeva and H.M. Mitchison and F. Muntoni and A. Onoufriadis and V. Parker and F. Payne and F.L. Raymond and N. Roberts and D.B. Savage and P. Scambler and M. Schmidts and N. Schoenmakers and R.K. Semple and E. Serra and O. Spasic-Boskovic and E. Stevens and {Van Kogelenberg}, M. and P. Vijayarangakannan and K.A. Williamson and C. Wilson and T. Whyte and A. Ciampi and K. Oualkacha and M. Bobrow and H. Griffin and J. Kaye and K. Kennedy and A. Kent and C. Smee and R. Charlton and R. Ekong and F. Khawaja and L.R. Lopes and N. Migone and S.J. Payne and R.C. Pollitt and S. Povey and C.K. Ridout and R.L. Robinson and R.H. Scott and A. Shaw and P. Syrris and R. Taylor and A.M. Vandersteen and A. Amuzu and J.P. Casas and J.C. Chambers and G. Dedoussis and G. Gambaro and P. Gasparini and A. Isaacs and J. Johnson and M.E. Kleber and J.S. Kooner and C. Langenberg and J. Luan and G. Malerba and W. M{\"a}rz and A. Matchan and R. Morris and B.G. Nordestgaard and M. Benn and R.A. Scott and D. Toniolo and M. Traglia and A. Tybjaerg-Hansen and {Van Duijn}, C.M. and {Van Leeuwen}, E.M. and A. Varbo and P. Whincup and G. Zaza and W. Zhang",
year = "2015",
doi = "10.1038/nature14962",
language = "English",
volume = "526",
pages = "82--89",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group - Macmillan Publishers",
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, 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, S-Y, 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, S, Yang, J, Zhang, F, Zheng, H-F, 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

The UK10K project identifies rare variants in health and disease. / 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.; Hurles, M.E.; Zeggini, E.; Barrett, J.C.; Plagnol, V.; Richards, J.B.; Greenwood, C.M.T.; Timpson, N.J.; Durbin, R.; Bala, S.; Clapham, P.; Coates, G.; Cox, T.; Daly, A.; Du, Y.; Edkins, S.; Ellis, P.; Flicek, P.; Guo, X.; Huang, L.; Jackson, D.K.; Joyce, C.; Keane, T.; Kolb-Kokocinski, A.; Langford, C.; Li, Y.; Liang, J.; Lin, H.; Liu, R.; Maslen, J.; Muddyman, D.; Quail, M.A.; 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, G.D.; Day, I.N.M.; Day-Williams, A.; Down, T.; Dunham, I.; Evans, D.M.; Gaunt, T.R.; Geihs, M.; Hart, D.; Howie, B.; Hubbard, T.; Hysi, P.; Jamshidi, Y.; Karczewski, K.J.; Kemp, J.P.; Lachance, G.; Lek, M.; Lopes, M.; Macarthur, D.G.; Marchini, J.; Mangino, M.; Mathieson, I.; Metrustry, S.; Moayyeri, A.; Northstone, K.; Panoutsopoulou, K.; Paternoster, L.; Quaye, L.; Ring, S.; Ritchie, G.R.S.; Shihab, H.A.; Shin, S.-Y.; Small, K.S.; Artigas, M.S.; Soranzo, N.; Southam, L.; Spector, T.D.; St Pourcain, B.; Surdulescu, G.; Tachmazidou, I.; Tobin, M.D.; Valdes, A.M.; Visscher, P.M.; Ward, K.; Wilson, Scott; Yang, J.; Zhang, F.; Zheng, H.-F.; Anney, R.; Ayub, M.; Blackwood, D.; Bolton, P.F.; Breen, G.; Collier, D.A.; Craddock, N.; Curran, S.; Curtis, D.; Gallagher, L.; Geschwind, D.; Gurling, H.; Holmans, P.; Lee, I.; Lönnqvist, J.; Mcguffin, P.; Mcintosh, A.M.; Mckechanie, A.G.; Mcquillin, A.; Morris, J.; O'Donovan, M.C.; Owen, M.J.; Palotie, A.; Parr, J.R.; Paunio, T.; Pietilainen, O.; Rehnström, K.; Sharp, S.I.; Skuse, D.; St Clair, D.; Suvisaari, J.; Walters, J.T.R.; Williams, H.J.; Bochukova, E.; Bounds, R.; Dominiczak, A.; Farooqi, I.S.; Keogh, J.; Marenne, G.; Morris, A.; O'Rahilly, S.; Porteous, D.J.; Smith, B.H.; Wheeler, E.; Al Turki, S.; Anderson, C.A.; Antony, D.; Beales, P.; Bentham, J.; Bhattacharya, S.; Calissano, M.; Carss, K.; Chatterjee, K.; Cirak, S.; Cosgrove, C.; Fitzpatrick, D.R.; Foley, A.R.; Franklin, C.S.; Grozeva, D.; Mitchison, H.M.; Muntoni, F.; Onoufriadis, A.; Parker, V.; Payne, F.; Raymond, F.L.; Roberts, N.; Savage, D.B.; Scambler, P.; Schmidts, M.; Schoenmakers, N.; Semple, R.K.; Serra, E.; Spasic-Boskovic, O.; Stevens, E.; Van Kogelenberg, M.; Vijayarangakannan, P.; Williamson, K.A.; 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, L.R.; Migone, N.; Payne, S.J.; Pollitt, R.C.; Povey, S.; Ridout, C.K.; Robinson, R.L.; Scott, R.H.; Shaw, A.; Syrris, P.; Taylor, R.; Vandersteen, A.M.; Amuzu, A.; Casas, J.P.; Chambers, J.C.; Dedoussis, G.; Gambaro, G.; Gasparini, P.; Isaacs, A.; Johnson, J.; Kleber, M.E.; Kooner, J.S.; Langenberg, C.; Luan, J.; Malerba, G.; März, W.; Matchan, A.; Morris, R.; Nordestgaard, B.G.; Benn, M.; Scott, R.A.; Toniolo, D.; Traglia, M.; Tybjaerg-Hansen, A.; Van Duijn, C.M.; Van Leeuwen, E.M.; Varbo, A.; Whincup, P.; Zaza, G.; Zhang, W.

In: Nature, Vol. 526, No. 7571, 2015, p. 82-89.

Research output: Contribution to journal › Article

TY - JOUR

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

AU - Walter, K.

AU - Min, J.L.

AU - Huang, J.

AU - Crooks, L.

AU - Memari, Y.

AU - Mccarthy, S.

AU - Perry, J.R.B.

AU - Xu, C.

AU - Futema, M.

AU - Lawson, D.

AU - Iotchkova, V.

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PY - 2015

Y1 - 2015

N2 - © 2015 Macmillan Publishers Limited. All rights reserved. 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 - © 2015 Macmillan Publishers Limited. All rights reserved. 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.

U2 - 10.1038/nature14962

DO - 10.1038/nature14962

M3 - Article

VL - 526

SP - 82

EP - 89

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7571

ER -

Walter K, Min JL, Huang J, Crooks L, Memari Y, Mccarthy S et al. The UK10K project identifies rare variants in health and disease. Nature. 2015;526(7571):82-89. https://doi.org/10.1038/nature14962

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