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

Manuel A. Ferreira; Judith M. Vonk; Hansjorg Baurecht; Ingo Marenholz; Chao Tian; Joshua D. Hoffman; Quinta Helmer; Annika Tillander; Vilhelmina Ullemar; Jenny van Dongen; Yi Lu; Franz Rueschendorf; 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 Rodriguez; 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 Loset; 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 Huebner; 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; 23andMe Research Team; AAGC collaborators; BIOS consortium; LifeLines Cohort Study

doi:10.1038/ng.3985

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

Manuel A. Ferreira, Judith M. Vonk, Hansjorg Baurecht, Ingo Marenholz, Chao Tian, Joshua D. Hoffman, Quinta Helmer, Annika Tillander, Vilhelmina Ullemar, Jenny van Dongen, Yi Lu, Franz Rueschendorf, Jorge Esparza-Gordillo, Chris W. Medway, Edward Mountjoy, Kimberley Burrows, Oliver Hummel, Sarah Grosche, Ben M. Brumpton, John S. WitteJouke-Jan Hottenga, Gonneke Willemsen, Jie Zheng, Elke Rodriguez, 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 Loset, 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 Huebner, 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, 23andMe Research Team, AAGC collaborators, BIOS consortium, LifeLines Cohort Study

UWA Medical School

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

375 Citations (Scopus)

Abstract

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals(1), partly because of a shared genetic origin(2-4). 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 x 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.

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

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10.1038/ng.3985

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989923

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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., Rueschendorf, F., Esparza-Gordillo, J., Medway, C. W., Mountjoy, E., Burrows, K., Hummel, O., Grosche, S., Brumpton, B. M., ... LifeLines Cohort Study (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{97f9fbd9c01049afabb86c0c3f4f2fd5,

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(1), partly because of a shared genetic origin(2-4). 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 x 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.",

keywords = "GENOME-WIDE ASSOCIATION, LD SCORE REGRESSION, ATOPIC-DERMATITIS, HUMAN-CELLS, VARIANTS, IDENTIFICATION, RHINITIS, COHORT, TWIN, TRANSCRIPTOME",

author = "Ferreira, {Manuel A.} and Vonk, {Judith M.} and Hansjorg 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 Rueschendorf 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 Jouke-Jan Hottenga and Gonneke Willemsen and Jie Zheng and Elke Rodriguez 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 Loset 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 Huebner and Stephan Weidinger and Magnusson, {Patrik K. E.} and Rick Jansen and Eric Jorgenson and Young-Ae Lee and Boomsma, {Dorret I.} and Catarina Almqvist and Robert Karlsson and Koppelman, {Gerard H.} and Lavinia Paternoster and {23andMe Research Team} and {AAGC collaborators} and {BIOS consortium} and {LifeLines Cohort Study}",

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 Publishing Group - Macmillan Publishers",

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, Rueschendorf, F, Esparza-Gordillo, J, Medway, CW, Mountjoy, E, Burrows, K, Hummel, O, Grosche, S, Brumpton, BM, Witte, JS, Hottenga, J-J, Willemsen, G, Zheng, J, Rodriguez, 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, Loset, 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, Huebner, N, Weidinger, S, Magnusson, PKE, Jansen, R, Jorgenson, E, Lee, Y-A, Boomsma, DI, Almqvist, C, Karlsson, R, Koppelman, GH, Paternoster, L, 23andMe Research Team, AAGC collaborators, BIOS consortium & LifeLines Cohort Study 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, Hansjorg

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 - Rueschendorf, 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 - Rodriguez, 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 - Loset, 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 - Huebner, 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

AU - 23andMe Research Team

AU - AAGC collaborators

AU - BIOS consortium

AU - LifeLines Cohort Study

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(1), partly because of a shared genetic origin(2-4). 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 x 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.

AB - Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals(1), partly because of a shared genetic origin(2-4). 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 x 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.

KW - GENOME-WIDE ASSOCIATION

KW - LD SCORE REGRESSION

KW - ATOPIC-DERMATITIS

KW - HUMAN-CELLS

KW - VARIANTS

KW - IDENTIFICATION

KW - RHINITIS

KW - COHORT

KW - TWIN

KW - TRANSCRIPTOME

U2 - 10.1038/ng.3985

DO - 10.1038/ng.3985

M3 - Letter

C2 - 29083406

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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