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Journal Article

New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries

Authors

  1. Nick Shrine
  2. Anna L. Guyatt
  3. A. Mesut Erzurumluoglu
  4. Victoria E. Jackson
  5. Brian D. Hobbs
  6. Carl A. Melbourne
  7. Chiara Batini
  8. Katherine A. Fawcett
  9. Kijoung Song
  10. Phuwanat Sakornsakolpat
  11. Xingnan Li
  12. Ruth Boxall
  13. Nicola F. Reeve
  14. Ma'en Obeidat
  15. Jing Hua Zhao
  16. Matthias Wielscher
  17. Stefan Weiss
  18. Katherine A. Kentistou
  19. James P. Cook
  20. Benjamin B. Sun
  21. Jian Zhou
  22. Jennie Hui
  23. Stefan Karrasch
  24. Medea Imboden
  25. Sarah E. Harris
  26. Jonathan Marten
  27. Stefan Enroth
  28. Shona M. Kerr
  29. Ida Surakka
  30. Veronique Vitart
  31. Terho Lehtimäki
  32. Richard J. Allen
  33. Per S. Bakke
  34. Terri H. Beaty
  35. Eugene R. Bleecker
  36. Yohan Bossé
  37. Corry-Anke Brandsma
  38. Zhengming Chen
  39. James D. Crapo
  40. John Danesh
  41. Dawn L. DeMeo
  42. Frank Dudbridge
  43. Ralf Ewert
  44. Christian Gieger
  45. Amund Gulsvik
  46. Anna L. Hansell
  47. Ke Hao
  48. Joshua D. Hoffman
  49. John E. Hokanson
  50. Georg Homuth
  51. Peter K. Joshi
  52. Philippe Joubert
  53. Claudia Langenberg
  54. Xuan Li
  55. Liming Li
  56. Kuang Lin
  57. Lars Lind
  58. Nicholas Locantore
  59. Jian’an Luan
  60. Anubha Mahajan
  61. Joseph C. Maranville
  62. Alison Murray
  63. David C. Nickle
  64. Richard Packer
  65. Margaret M. Parker
  66. Megan L. Paynton
  67. David J. Porteous
  68. Dmitry Prokopenko
  69. Dandi Qiao
  70. Rajesh Rawal
  71. Heiko Runz
  72. Ian Sayers
  73. Don D. Sin
  74. Blair H. Smith
  75. María Soler Artigas
  76. David Sparrow
  77. Ruth Tal-Singer
  78. Paul R. H. J. Timmers
  79. Maarten Van den Berge
  80. John C. Whittaker
  81. Prescott G. Woodruff
  82. Laura M. Yerges-Armstrong
  83. Olga G. Troyanskaya
  84. Olli T. Raitakari
  85. Mika Kähönen
  86. Ozren Polašek
  87. Ulf Gyllensten
  88. Igor Rudan
  89. Ian J. Deary
  90. Nicole M. Probst-Hensch
  91. Holger Schulz
  92. Alan L. James
  93. James F. Wilson
  94. Beate Stubbe
  95. Eleftheria Zeggini
  96. Marjo-Riitta Jarvelin
  97. Nick Wareham
  98. Edwin K. Silverman
  99. Caroline Hayward
  100. Andrew P. Morris
  101. Adam S. Butterworth
  102. Robert A. Scott
  103. Robin G. Walters
  104. Deborah A. Meyers
  105. Michael H. Cho
  106. David P. Strachan
  107. Ian P. Hall
  108. Martin D. Tobin
  109. Louise V. Wain

Publication date

25 Feb 2019

Summary

Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function–associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.

Published in

Nature Genetics

Volume and page numbers

51 , 481 -493

DOI

https://doi.org/10.1038/s41588-018-0321-7

ISSN

16

Subjects

Health, Biology, and Genetics

Notes

University of Essex, Albert Sloman Library *University of Essex registered users - Campus access*


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