Article open access publication

The UK10K project identifies rare variants in health and disease

Nature, Springer Nature, ISSN 1476-4687

Volume 526, 7571, 2015

DOI:10.1038/nature14962, Dimensions: pub.1049666571, PMC: PMC4773891, PMID: 26367797,

Authors

Crooks, Lucy (1) (3)
Xu, ChangJiang (6) (7)
Li, Rui (6) (7)
Floyd, James (1) (11)
Barroso, Inês (1) (13) (14)
Brent Richards, J. (5) (6) (7)
Soranzo, Nicole * (1) (13)
Cox, Tony (1)
Flicek, Paul R (1) (9)
Guo, Xiaosen (15) (16)
Lin, Hong (15)
Liu, Ryan (17)
Sun, Jianping (6) (7)
Tian, Jing (15)
Wang, Jun (15) (16) (18) (19) (20)
Wang, Yu (15)
Wong, Kim (1)
Barroso, Inês (1) (13) (14)
Chen, Lu (1) (13)
Down, Thomas A (1) (5) (25)
Evans, David M (2) (26)
Hubbard, Tim J P (1) (5) (25)
Kemp, John Peter (2) (26)
Lopes, Margarida (1) (31) (32)
Marchini, Jonathan (32) (33)
Mangino, Massimo (5) (34)
Brent Richards, J. (5) (6) (7)
Shin, So-Youn (1) (2)
Soranzo, Nicole * (1) (13)
Tobin, Martin D (12) (36)
Wilson, Scott G (5) (37) (38)
Wong, Kim (1)
Yang, Jian (26)
Zheng, Hou-Feng (6) (7)
Crooks, Lucy (1) (3)
Curran, Sarah R (5) (44) (45)
Palotie, Aarno (1) (30) (48)
Paunio, Tiina (47) (50)
Pietiläinen, Olli P H (1) (47) (48)
Barroso, Inês (1) (13) (14)
Bochukova, Elena G (13) (14)
Bounds, Rebecca (13) (14)
Farooqi, I. Sadaf (13) (14)
Keogh, Julia M (13) (14)
O'Rahilly, Stephen (13) (14)
Barroso, Inês (1) (13) (14)
Floyd, James (1) (11)
O'Rahilly, Stephen (13) (14)
Parker, Victoria (13) (14)
Schmidts, Miriam (8) (57)
Semple, Robert K. (13) (14)
Li, Rui (6) (7)
Xu, ChangJiang (6) (7)
Kaye, Jane (33)
Kennedy, Karen (1) (59)
Semple, Robert K. (13) (14)
Shaw, Adam (66)
Barroso, Inês (1) (13) (14)
Farooqi, I. Sadaf (13) (14)
Kaye, Jane (33)
Kennedy, Karen (1) (59)
Palotie, Aarno (1) (30) (48)
Brent Richards, J. (5) (6) (7)
Soranzo, Nicole * (1) (13)
Gasparini, Paolo P (22) (23) (72)
März, Winfried (77) (78) (79)
Benn, Marianne (16) (81)
Soranzo, Nicole * (1) (13)
Varbo, Anette (16) (81)

* Corresponding author

Affiliations

Organisations

  1. (1) Wellcome Sanger Institute, grid.10306.34
  2. (2) University of Bristol, grid.5337.2
  3. (3) Sheffield Children's NHS Foundation Trust, grid.419127.8
  4. (4) MRC Epidemiology Unit, grid.415056.3
  5. (5) King's College London, grid.13097.3c
  6. (6) McGill University, grid.14709.3b
  7. (7) Jewish General Hospital, grid.414980.0
  8. (8) University College London, grid.83440.3b
  9. (9) European Bioinformatics Institute, grid.225360.0
  10. (10) University of Colorado Denver, grid.241116.1
  11. (11) University of London, grid.4464.2
  12. (12) University of Leicester, grid.9918.9
  13. (13) University of Cambridge, grid.5335.0
  14. (14) Addenbrooke's Hospital, grid.120073.7
  15. (15) Beijing Genomics Institute, grid.21155.32
  16. (16) University of Copenhagen, grid.5254.6, KU
  17. (17) BGI-Europe, EC2M 4YE, London, UK
  18. (18) King Abdulaziz University, grid.412125.1
  19. (19) Macau University of Science and Technology, grid.259384.1
  20. (20) University of Hong Kong, grid.194645.b
  21. (21) National Health Service, grid.451052.7
  22. (22) Medical Genetics, Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, 34100, Trieste, Italy
  23. (23) University of Trieste, grid.5133.4
  24. (24) Biogen (United States), grid.417832.b
  25. (25) Guy's Hospital, grid.239826.4
  26. (26) University of Queensland, grid.1003.2
  27. (27) Adaptive Biotechnologies (United States), grid.421940.a
  28. (28) St George's, University of London, grid.264200.2
  29. (29) Massachusetts General Hospital, grid.32224.35
  30. (30) Broad Institute, grid.66859.34
  31. (31) Illumina (United Kingdom), grid.434747.7
  32. (32) Wellcome Centre for Human Genetics, grid.270683.8
  33. (33) University of Oxford, grid.4991.5
  34. (34) National Institute for Health Research, grid.451056.3
  35. (35) Harvard University, grid.38142.3c
  36. (36) Glenfield Hospital, grid.412925.9
  37. (37) Sir Charles Gairdner Hospital, grid.3521.5
  38. (38) University of Western Australia, grid.1012.2
  39. (39) St. James's Hospital, grid.416409.e
  40. (40) Queen's University, grid.410356.5
  41. (41) University of Edinburgh, grid.4305.2
  42. (42) Eli Lilly (United Kingdom), grid.418786.4
  43. (43) Cardiff University, grid.5600.3
  44. (44) Sussex Partnership NHS Foundation Trust, grid.451317.5
  45. (45) University of Sussex, grid.12082.39
  46. (46) University of California, Los Angeles, grid.19006.3e
  47. (47) Finnish Institute for Health and Welfare, grid.14758.3f
  48. (48) Institute for Molecular Medicine Finland, grid.452494.a
  49. (49) Newcastle University, grid.1006.7
  50. (50) University of Helsinki, grid.7737.4
  51. (51) University of Aberdeen, grid.7107.1
  52. (52) University of Glasgow, grid.8756.c
  53. (53) Western General Hospital, grid.417068.c
  54. (54) Ninewells Hospital, grid.416266.1
  55. (55) King Abdulaziz Medical City, grid.415254.3
  56. (56) University Hospital Cologne, grid.411097.a
  57. (57) Radboud Institute for Molecular Life Sciences, grid.461760.2
  58. (58) University of Quebec at Montreal, grid.38678.32
  59. (59) National Cancer Research Institute, grid.451262.6
  60. (60) Genetic Alliance UK (United Kingdom), grid.434654.4
  61. (61) St James's University Hospital, grid.443984.6
  62. (62) University of Lisbon, grid.9983.b
  63. (63) University of Turin, grid.7605.4
  64. (64) Northwick Park Hospital, grid.416568.8
  65. (65) Great Ormond Street Hospital, grid.420468.c
  66. (66) Guy's and St Thomas' NHS Foundation Trust, grid.420545.2
  67. (67) Maritime Medical Genetics Service, 5850/5980 University Avenue, PO Box 9700, B3K 6R8, Halifax, Nova Scotia, Canada
  68. (68) London School of Hygiene & Tropical Medicine, grid.8991.9
  69. (69) Imperial College London, grid.7445.2
  70. (70) Harokopio University, grid.15823.3d
  71. (71) Catholic University of the Sacred Heart, grid.8142.f
  72. (72) Experimental Genetics Division, Sidra, P.O. Box 26999, Doha, Qatar
  73. (73) Erasmus MC, grid.5645.2
  74. (74) Vth Department of Medicine, Medical Faculty, 68167, Mannheim, Germany
  75. (75) Institute of Metabolic Science, grid.470900.a
  76. (76) University of Verona, grid.5611.3
  77. (77) Heidelberg University, grid.7700.0
  78. (78) Medical University of Graz, grid.11598.34
  79. (79) Synlab (Germany), grid.461810.a
  80. (80) School of Social and Community Medicine, Canynge Hall, 39 Whatley Road, BS8 2PS, Bristol, UK
  81. (81) Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730, Herlev, Denmark
  82. (82) San Raffaele Hospital, grid.18887.3e
  83. (83) Rigshospitalet, grid.475435.4, Capital Region

Description

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.

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University of Copenhagen

Danish Open Access Indicator

2015: Realized

Research area: Science & Technology

Danish Bibliometrics Indicator

2015: Level 2

Research area: Science & Technology

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Times Cited: 733

Field Citation Ratio (FCR): 90.73

Relative Citation ratio (RCR): 20.09

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Hybrid