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

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; Jorge Esparza-Gordillo; Chris W. Medway; Edward Mountjoy; Kimberley Burrows; Oliver Hummel; Sarah Grosche; Ben M. Brumpton; John S. Witte; Jouke Jan Hottenga; Gonneke Willemsen; Jie Zheng; Elke Rodríguez; Melanie Hotze; Andre Franke; Joana A. Revez; Jonathan Beesley; Melanie C. Matheson; Shyamali C. Dharmage; Lisa M. Bain; Lars G. Fritsche; Maiken E. Gabrielsen; Brunilda Balliu; Jonas B. Nielsen; Wei Zhou; Kristian Hveem; Arnulf Langhammer; Oddgeir L. Holmen; Mari Løset; Goncalo R. Abecasis; Cristen J. Willer; Andreas Arnold; Georg Homuth; Carsten O. Schmidt; Philip J. Thompson; Nicholas G. Martin; David L. Duffy; Natalija Novak; Holger Schulz; Stefan Karrasch; Christian Gieger; Konstantin Strauch; Ronald B. Melles; David A. Hinds; 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

doi:10.1038/ng.3985

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

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
, Jorge Esparza-Gordillo
, Chris W. Medway
, Edward Mountjoy
, Kimberley Burrows
, Oliver Hummel
, Sarah Grosche
, Ben M. Brumpton
, John S. Witte

Jouke Jan Hottenga, Gonneke Willemsen, Jie Zheng, Elke Rodríguez, Melanie Hotze, Andre Franke, Joana A. Revez, Jonathan Beesley, Melanie C. Matheson, Shyamali C. Dharmage, Lisa M. Bain, Lars G. Fritsche, Maiken E. Gabrielsen, Brunilda Balliu, Jonas B. Nielsen, Wei Zhou, Kristian Hveem, Arnulf Langhammer, Oddgeir L. Holmen, Mari Løset, Goncalo R. Abecasis, Cristen J. Willer, Andreas Arnold, Georg Homuth, Carsten O. Schmidt, Philip J. Thompson, Nicholas G. Martin, David L. Duffy, Natalija Novak, Holger Schulz, Stefan Karrasch, Christian Gieger, Konstantin Strauch, Ronald B. Melles, David A. Hinds, 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

^*Corresponding author for this work

Queensland Institute of Medical Research
University of Groningen
University Hospital of Schleswig-Holstein
Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Charité – Universitätsmedizin Berlin
Research 23 and Me
University of California at San Francisco
Vrije Universiteit Amsterdam
Karolinska Institutet
GlaxoSmithKline
University of Bristol
Norwegian University of Science and Technology
Kiel University
University of Melbourne
Stanford University
University of Michigan, Ann Arbor
University of Greifswald
University of Western Australia
University of Bonn
Helmholtz Zentrum München - German Research Center for Environmental Health
Member of the German Center for Lung Research
Ludwig Maximilian University of Munich
Kaiser Permanente
VU University Medical Center

Research output: Contribution to journal › Article › peer-review

420 Citations (Scopus)

Abstract

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. 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 â8), 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.

Original language	English
Pages (from-to)	1752-1757
Number of pages	6
Journal	Nature Genetics
Volume	49
Issue number	12
DOIs	https://doi.org/10.1038/ng.3985
Publication status	Published - 1 Dec 2017
Externally published	Yes

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Ferreira, M. A., Vonk, J. M., Baurecht, H., Marenholz, I., Tian, C., Hoffman, J. D., Helmer, Q., Tillander, A., Ullemar, V., Van Dongen, J., Lu, Y., Rüschendorf, F., Esparza-Gordillo, J., Medway, C. W., Mountjoy, E., Burrows, K., Hummel, O., Grosche, S., Brumpton, B. M., ... Paternoster, L. (2017). Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology. Nature Genetics, 49(12), 1752-1757. https://doi.org/10.1038/ng.3985

@article{f533329f4f7643e6829e30342e12d027,

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

abstract = "Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. 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 {\^a}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.",

author = "Ferreira, \{Manuel A.\} and Vonk, \{Judith M.\} and Hansj{\"o}rg Baurecht and Ingo Marenholz and Chao Tian and Hoffman, \{Joshua D.\} and Quinta Helmer and Annika Tillander and Vilhelmina Ullemar and \{Van Dongen\}, Jenny and Yi Lu and Franz R{\"u}schendorf and Jorge Esparza-Gordillo and Medway, \{Chris W.\} and Edward Mountjoy and Kimberley Burrows and Oliver Hummel and Sarah Grosche and Brumpton, \{Ben M.\} and Witte, \{John S.\} and Hottenga, \{Jouke Jan\} and Gonneke Willemsen and Jie Zheng and Elke Rodr{\'i}guez and Melanie Hotze and Andre Franke and Revez, \{Joana A.\} and Jonathan Beesley and Matheson, \{Melanie C.\} and Dharmage, \{Shyamali C.\} and Bain, \{Lisa M.\} and Fritsche, \{Lars G.\} and Gabrielsen, \{Maiken E.\} and Brunilda Balliu and Nielsen, \{Jonas B.\} and Wei Zhou and Kristian Hveem and Arnulf Langhammer and Holmen, \{Oddgeir L.\} and Mari L{\o}set and Abecasis, \{Goncalo R.\} and Willer, \{Cristen J.\} and Andreas Arnold and Georg Homuth and Schmidt, \{Carsten O.\} and Thompson, \{Philip J.\} and Martin, \{Nicholas G.\} and Duffy, \{David L.\} and Natalija Novak and Holger Schulz and Stefan Karrasch and Christian Gieger and Konstantin Strauch and Melles, \{Ronald B.\} and Hinds, \{David A.\} and Norbert H{\"u}bner and Stephan Weidinger and Magnusson, \{Patrik K.E.\} and Rick Jansen and Eric Jorgenson and Lee, \{Young Ae\} and Boomsma, \{Dorret I.\} and Catarina Almqvist and Robert Karlsson and Koppelman, \{Gerard H.\} and Lavinia Paternoster",

note = "Publisher Copyright: {\textcopyright} 2017 Nature America, Inc.",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/ng.3985",

language = "English",

volume = "49",

pages = "1752--1757",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "12",

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Ferreira, MA, Vonk, JM, Baurecht, H, Marenholz, I, Tian, C, Hoffman, JD, Helmer, Q, Tillander, A, Ullemar, V, Van Dongen, J, Lu, Y, Rüschendorf, F, Esparza-Gordillo, J, Medway, CW, Mountjoy, E, Burrows, K, Hummel, O, Grosche, S, Brumpton, BM, Witte, JS, Hottenga, JJ, Willemsen, G, Zheng, J, Rodríguez, E, Hotze, M, Franke, A, Revez, JA, Beesley, J, Matheson, MC, Dharmage, SC, Bain, LM, Fritsche, LG, Gabrielsen, ME, Balliu, B, Nielsen, JB, Zhou, W, Hveem, K, Langhammer, A, Holmen, OL, Løset, M, Abecasis, GR, Willer, CJ, Arnold, A, Homuth, G, Schmidt, CO, Thompson, PJ, Martin, NG, Duffy, DL, Novak, N, Schulz, H, Karrasch, S, Gieger, C, Strauch, K, Melles, RB, Hinds, DA, Hübner, N, Weidinger, S, Magnusson, PKE, Jansen, R, Jorgenson, E, Lee, YA, Boomsma, DI, Almqvist, C, Karlsson, R, Koppelman, GH & Paternoster, L 2017, 'Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology', Nature Genetics, vol. 49, no. 12, pp. 1752-1757. https://doi.org/10.1038/ng.3985

TY - JOUR

T1 - Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology

AU - Ferreira, Manuel A.

AU - Vonk, Judith M.

AU - Baurecht, Hansjörg

AU - Marenholz, Ingo

AU - Tian, Chao

AU - Hoffman, Joshua D.

AU - Helmer, Quinta

AU - Tillander, Annika

AU - Ullemar, Vilhelmina

AU - Van Dongen, Jenny

AU - Lu, Yi

AU - Rüschendorf, Franz

AU - Esparza-Gordillo, Jorge

AU - Medway, Chris W.

AU - Mountjoy, Edward

AU - Burrows, Kimberley

AU - Hummel, Oliver

AU - Grosche, Sarah

AU - Brumpton, Ben M.

AU - Witte, John S.

AU - Hottenga, Jouke Jan

AU - Willemsen, Gonneke

AU - Zheng, Jie

AU - Rodríguez, Elke

AU - Hotze, Melanie

AU - Franke, Andre

AU - Revez, Joana A.

AU - Beesley, Jonathan

AU - Matheson, Melanie C.

AU - Dharmage, Shyamali C.

AU - Bain, Lisa M.

AU - Fritsche, Lars G.

AU - Gabrielsen, Maiken E.

AU - Balliu, Brunilda

AU - Nielsen, Jonas B.

AU - Zhou, Wei

AU - Hveem, Kristian

AU - Langhammer, Arnulf

AU - Holmen, Oddgeir L.

AU - Løset, Mari

AU - Abecasis, Goncalo R.

AU - Willer, Cristen J.

AU - Arnold, Andreas

AU - Homuth, Georg

AU - Schmidt, Carsten O.

AU - Thompson, Philip J.

AU - Martin, Nicholas G.

AU - Duffy, David L.

AU - Novak, Natalija

AU - Schulz, Holger

AU - Karrasch, Stefan

AU - Gieger, Christian

AU - Strauch, Konstantin

AU - Melles, Ronald B.

AU - Hinds, David A.

AU - Hübner, Norbert

AU - Weidinger, Stephan

AU - Magnusson, Patrik K.E.

AU - Jansen, Rick

AU - Jorgenson, Eric

AU - Lee, Young Ae

AU - Boomsma, Dorret I.

AU - Almqvist, Catarina

AU - Karlsson, Robert

AU - Koppelman, Gerard H.

AU - Paternoster, Lavinia

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. 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 â8), 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.

AB - Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. 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 â8), 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.

UR - https://www.scopus.com/pages/publications/85035776645

U2 - 10.1038/ng.3985

DO - 10.1038/ng.3985

M3 - Article

C2 - 29083406

AN - SCOPUS:85035776645

SN - 1061-4036

VL - 49

SP - 1752

EP - 1757

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

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

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