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Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology

Nature Genetics volume 49, pages 17521757 (2017) | Download Citation


Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals1, partly because of a shared genetic origin2,3,4. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10−8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.

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This research was conducted using the UK Biobank resource under application number 10074. Detailed acknowledgments and funding details are provided for each contributing study in the Supplementary Note.

Author information

Author notes

    • Jorge Esparza-Gordillo

    Present address: GlaxoSmithKline, Stevenage, UK.

    • Manuel A Ferreira
    • , Judith M Vonk
    • , Hansjörg Baurecht
    • , Ingo Marenholz
    • , Chao Tian
    • , Joshua D Hoffman
    • , Quinta Helmer
    • , Annika Tillander
    • , Vilhelmina Ullemar
    • , Jenny van Dongen
    • , Yi Lu
    •  & Franz Rüschendorf

    These authors contributed equally to this work.

    • Norbert Hübner
    • , Stephan Weidinger
    • , Patrik K E Magnusson
    • , Rick Jansen
    • , Eric Jorgenson
    • , Young-Ae Lee
    • , Dorret I Boomsma
    • , Catarina Almqvist
    • , Robert Karlsson
    • , Gerard H Koppelman
    •  & Lavinia Paternoster

    These authors jointly supervised this work.


  1. Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

    • Manuel A Ferreira
    • , Joana A Revez
    • , Jonathan Beesley
    • , Lisa M Bain
    • , Nicholas G Martin
    •  & David L Duffy
  2. Epidemiology, University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands.

    • Judith M Vonk
  3. Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

    • Hansjörg Baurecht
    • , Elke Rodríguez
    • , Melanie Hotze
    •  & Stephan Weidinger
  4. Max Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.

    • Ingo Marenholz
    • , Franz Rüschendorf
    • , Jorge Esparza-Gordillo
    • , Oliver Hummel
    • , Sarah Grosche
    • , Norbert Hübner
    •  & Young-Ae Lee
  5. Clinic for Pediatric Allergy, Experimental and Clinical Research Center of Charité Universitätsmedizin Berlin and Max Delbrück Center, Berlin, Germany.

    • Ingo Marenholz
    • , Jorge Esparza-Gordillo
    • , Sarah Grosche
    •  & Young-Ae Lee
  6. Research, 23andMe, Mountain View, California, USA.

    • Chao Tian
    •  & David A Hinds
  7. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.

    • Joshua D Hoffman
  8. Department of Biological Psychology, Netherlands Twin Register, Vrije University, Amsterdam, the Netherlands.

    • Quinta Helmer
    • , Jenny van Dongen
    • , Jouke-Jan Hottenga
    • , Gonneke Willemsen
    •  & Dorret I Boomsma
  9. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    • Annika Tillander
    • , Vilhelmina Ullemar
    • , Yi Lu
    • , Patrik K E Magnusson
    • , Catarina Almqvist
    •  & Robert Karlsson
  10. MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.

    • Chris W Medway
    • , Edward Mountjoy
    • , Kimberley Burrows
    • , Ben M Brumpton
    • , Jie Zheng
    •  & Lavinia Paternoster
  11. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

    • Ben M Brumpton
    • , Lars G Fritsche
    • , Maiken E Gabrielsen
    • , Kristian Hveem
    • , Oddgeir L Holmen
    • , Mari Løset
    • , Gonçalo R Abecasis
    •  & Cristen J Willer
  12. Department of Thoracic Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

    • Ben M Brumpton
  13. Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.

    • John S Witte
  14. Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.

    • Andre Franke
  15. Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.

    • Melanie C Matheson
    •  & Shyamali C Dharmage
  16. Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.

    • Brunilda Balliu
  17. Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.

    • Jonas B Nielsen
    •  & Cristen J Willer
  18. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

    • Jonas B Nielsen
    • , Wei Zhou
    •  & Cristen J Willer
  19. HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

    • Kristian Hveem
    •  & Arnulf Langhammer
  20. Department of Dermatology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

    • Mari Løset
  21. Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.

    • Gonçalo R Abecasis
    •  & Cristen J Willer
  22. Clinic and Polyclinic of Dermatology, University Medicine Greifswald, Greifswald, Germany.

    • Andreas Arnold
  23. Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.

    • Georg Homuth
  24. Institute for Community Medicine, Study of Health in Pomerania/KEF, University Medicine Greifswald, Greifswald, Germany.

    • Carsten O Schmidt
  25. Institute for Respiratory Health, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia.

    • Philip J Thompson
  26. Department of Dermatology and Allergology, University Hospital Bonn, Bonn, Germany.

    • Natalija Novak
  27. Institute of Epidemiology I, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Holger Schulz
    •  & Stefan Karrasch
  28. Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Munich, Germany.

    • Holger Schulz
    •  & Stefan Karrasch
  29. Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-Universität, Munich, Germany.

    • Stefan Karrasch
  30. Research Unit of Molecular Epidemiology and Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Christian Gieger
  31. Institute of Genetic Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Konstantin Strauch
  32. Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.

    • Ronald B Melles
    •  & Eric Jorgenson
  33. Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.

    • Rick Jansen
  34. Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.

    • Catarina Almqvist
  35. University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands.

    • Gerard H Koppelman


  1. 23andMe Research Team

    A full list of members and affiliations appears in the Supplementary Note.

  2. AAGC collaborators

    A full list of members and affiliations appears in the Supplementary Note.

  3. BIOS consortium

    A full list of members and affiliations appears in the Supplementary Note.

  4. LifeLines Cohort Study

    A full list of members and affiliations appears in the Supplementary Note.


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Data collection and analysis in the contributing studies: M.A.F., M.C.M., S.C.D., L.M.B., P.J.T., N.G.M., D.L.D. (AAGC study); J.M.V., G.H.K. (LifeLines study); H.B., E.R., M.H., A.F., N.N., H.S., S.K., C.G., K.S., S.W. (GENEVA study); I.M., F.R., J.E.-G., S.G., A.A., G.H., C.O.S., N.H., Y.-A.L. (GENUFAD studies); C.T., D.A.H. (23andMe study); J.D.H., J.S.W., R.B.M., E.J. (GERA study); Q.H., J.-J.H., G.W., D.I.B. (NTR study); A.T., V.U., Y.L., P.K.E.M., C.A., R.K. (CATSS, TWINGENE and SALTY studies); L.P. (ALSPAC study); B.M.B., L.G.F., M.E.G., J.B.N., W.Z., K.H., A.L., O.L.H., M.L., G.R.A., C.J.W. (HUNT study); L.P., M.A.F. (UK Biobank study). Methylation analysis: J.v.D., D.I.B., R.J. Biological and drug annotation: M.A.F., C.W.M., E.M., K.B., O.H., J.Z., J.A.R., J.B., B.B. Quality control, meta-analysis, tables and figures: M.A.F. Writing group: M.A.F., J.M.V., I.M., C.T., J.D.H., Q.H., A.T., V.U., J.v.D., Y.L., J.E.-G., B.M.B., J.B., S.C.D., S.W., P.K.E.M., R.J., E.J., Y.-A.L., D.I.B., C.A., R.K., G.H.K., L.P. Study design and management: M.A.F., D.A.H., B.M.B., S.W., P.K.E.M., R.J., E.J., Y.-A.L., D.I.B., C.A., R.K., G.H.K., L.P.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Manuel A Ferreira.

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    Supplementary Figures 1–6 and Supplementary Note

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    Supplementary Tables 1–29

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