Article open access publication

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Nature Genetics, Springer Nature, ISSN 1061-4036

Volume 50, 8, 2018

DOI:10.1038/s41588-018-0157-1, Dimensions: pub.1105604289, PMC: PMC7068780, PMID: 30013184,

Authors

Flores, Carlos (6) (7)
Antó, Josep M. (6) (11) (12) (13)
Curjuric, Ivan (23) (24)
Imboden, Medea (23) (24)
Jarvelin, Marjo-Riitta (10) (36) (37)
Kaprio, Jaakko (41) (42)
Kumar, Ashish (23) (24) (43)
Lee, Young-Ae (44) (45)
Melén, Erik (43) (46)
Mercader, Josep M. (17) (47) (48)
Pershagen, Göran (43) (51)
Pino-Yanes, Maria (6) (7) (34)
Stefansson, Kari (38) (39)
Torrents, David (17) (54)

* Corresponding author

Affiliations

Organisations

  1. (1) COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
  2. (2) Institute of Epidemiology, Helmholtz Zentrum München German Research Center for Environmental Health, Neuherberg, Germany
  3. (3) University of Manchester, grid.5379.8
  4. (4) 23andMe (United States), grid.420283.f
  5. (5) University of Chicago, grid.170205.1
  6. (6) Institute of Health Carlos III, grid.413448.e
  7. (7) Hospital Universitario Nuestra Señora de Candelaria, grid.411331.5
  8. (8) Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  9. (9) VU Amsterdam, grid.12380.38
  10. (10) Imperial College London, grid.7445.2
  11. (11) Hospital Del Mar, grid.411142.3
  12. (12) Pompeu Fabra University, grid.5612.0
  13. (13) Barcelona Institute for Global Health, grid.434607.2
  14. (14) University of Greifswald, grid.5603.0
  15. (15) Department of Dermatology, Venereology and Allergology, University-Hospital Schleswig-Hostein, Campus Kiel, Kiel, Germany
  16. (16) University of Arizona, grid.134563.6
  17. (17) Barcelona Supercomputing Center, grid.10097.3f
  18. (18) APH Amsterdam Public Health, Amsterdam, The Netherlands
  19. (19) Technical University of Denmark, grid.5170.3, DTU
  20. (20) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  21. (21) University of California, San Francisco, grid.266102.1
  22. (22) University of Southern California, grid.42505.36
  23. (23) Swiss Tropical and Public Health Institute, grid.416786.a
  24. (24) University of Basel, grid.6612.3
  25. (25) Erasmus University Medical Center, grid.5645.2
  26. (26) University of Melbourne, grid.1008.9
  27. (27) University of Liège, grid.4861.b
  28. (28) Ludwig Maximilian University of Munich, grid.5252.0
  29. (29) Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany
  30. (30) University of Bristol, grid.5337.2
  31. (31) Henry Ford Health System, grid.239864.2
  32. (32) University of Copenhagen, grid.5254.6, KU
  33. (33) Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University of Munich Medical Center, Ludwig-Maximilians-Universität München, Munich, Germany
  34. (34) University of La Laguna, grid.10041.34
  35. (35) Telethon Kids Institute, grid.414659.b
  36. (36) Oulu University Hospital, grid.412326.0
  37. (37) University of Oulu, grid.10858.34
  38. (38) University of Iceland, grid.14013.37
  39. (39) deCODE genetics/Amgen Inc, Reykjavik, Iceland
  40. (40) Kinderklinik Regensburg, grid.459443.b
  41. (41) National Institute for Health and Welfare, grid.14758.3f
  42. (42) University of Helsinki, grid.7737.4
  43. (43) Karolinska Institute, grid.4714.6
  44. (44) Charité, grid.6363.0
  45. (45) Max Delbrück Center for Molecular Medicine, grid.419491.0
  46. (46) Sachs' Children and Youth Hospital, grid.416452.0
  47. (47) Broad Institute, grid.66859.34
  48. (48) Massachusetts General Hospital, grid.32224.35
  49. (49) Institute of Clinical Research, University of Southern Denmark, Department of Obstetrics & Gynecology, Odense University Hospital, Odense, Denmark
  50. (50) University of Newcastle Australia, grid.266842.c
  51. (51) Stockholm County Council, grid.425979.4
  52. (52) Institute for Respiratory Health, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia
  53. (53) Institut d'Investigació Sanitària Illes Balears, grid.507085.f
  54. (54) Catalan Institution for Research and Advanced Studies, grid.425902.8
  55. (55) Brigham and Women's Hospital, grid.62560.37
  56. (56) QIMR Berghofer Medical Research Institute, grid.1049.c
  57. (57) University College London, grid.83440.3b

Description

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.

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Technical University of Denmark

University of Copenhagen

Danish Open Access Indicator

2018: Realized

Research area: Medicine

Danish Bibliometrics Indicator

2018: Level 3

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 26

Field Citation Ratio (FCR): 8.51

Relative Citation ratio (RCR): 2.09

Open Access Info

Green, Accepted