Shared genetic variants suggest common pathways in allergy and autoimmune diseases

Eskil Kreiner-Moller; Johannes Waage; Marie Standl; Susanne Brix; Tune H Pers; Alexessander Couto Alves; Nicole M. Warrington; Carla M T Tiesler; Elaine Fuertes; Lude Franke; Joel N Hirschhorn; Alan James; Angela Simpson; Joyce Y Tung; Gerard H Koppelman; Dirkje S Postma; Craig E Pennell; Marjo-Ritta Jarvelin; Adnan Custovic; Nicholas Timpson; Manuel A Ferreira; David P Strachan; John Henderson; David A Hinds; Hans Bisgaard; Klaus Bønnelykke

doi:10.1016/j.jaci.2016.10.055

Shared genetic variants suggest common pathways in allergy and autoimmune diseases

Eskil Kreiner-Moller, Johannes Waage, Marie Standl, Susanne Brix, Tune H Pers, Alexessander Couto Alves, Nicole M. Warrington, Carla M T Tiesler, Elaine Fuertes, Lude Franke, Joel N Hirschhorn, Alan James, Angela Simpson, Joyce Y Tung, Gerard H Koppelman, Dirkje S Postma, Craig E Pennell, Marjo-Ritta Jarvelin, Adnan Custovic, Nicholas TimpsonManuel A Ferreira, David P Strachan, John Henderson, David A Hinds, Hans Bisgaard, Klaus Bønnelykke

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Abstract

Background
The relationship between allergy and autoimmune disorders is complex and poorly understood.

Objective
To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms.

Methods
We meta-analyzed two GWAS on self-reported allergy and sensitization comprising a total of 62,330 individuals. These results were used to calculate enrichment for SNPs previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites, and characterized commonalities in the variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DHS data, and compared the allergy data with all known diseases.

Results
Among 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (p=1.4e-17) encompassing 29 loci at a false discovery rate<0.05. Such enrichment seemed to be a general characteristic for all autoimmune diseases. Among the common loci, 48% had the same direction of effect for allergy and autoimmune diseases. Additionally, we observed an enrichment of allergy SNPs falling within immune pathways and regions of chromatin accessible in immune cells that was also represented in autoimmune diseases, but not in other diseases.

Conclusion
We identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared diseases mechanisms. Further studies of these shared genetic mechanisms might help understanding the complex relationship between these diseases, including the parallel increase in disease prevalence.

Original language	English
Number of pages	11
Journal	Journal of Allergy and Clinical Immunology
Early online date	8 Feb 2017
DOIs	https://doi.org/10.1016/j.jaci.2016.10.055
Publication status	E-pub ahead of print - 8 Feb 2017

Keywords

Allergy
Single Nucleotide Polymorphism
Autoimmune Disease
Autoimmunity
Genetic Association Studies

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10.1016/j.jaci.2016.10.055

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This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Elsevier at https://doi.org/10.1016/j.jaci.2016.10.055 . Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 1.47 MBLicence: CC BY-NC-ND
Supplementary information PDF
This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Elsevier at https://doi.org/10.1016/j.jaci.2016.10.055 . Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 7.69 MBLicence: CC BY-NC-ND

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MRC UoB UNITE Unit - programme 3
Timpson, N. J. (Principal Investigator) & Timpson, N. J. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
THE NATURAL HISTORY OF ASTHMA AND WHEEZING ILLNESSES FROM BIRTH TO ADOLESCENCE: DETERMINANTS OF THE REMISSION OF ASTHMA
Henderson, A. J. W. (Principal Investigator)
1/10/06 → 1/10/10
Project: Research
EXTENSION OF RD1321 VIA IOP.
Golding, J. (Principal Investigator)
1/02/01 → 1/02/06
Project: Research

Cite this

Kreiner-Moller, E., Waage, J., Standl, M., Brix, S., Pers, T. H., Alves, A. C., Warrington, N. M., Tiesler, C. M. T., Fuertes, E., Franke, L., Hirschhorn, J. N., James, A., Simpson, A., Tung, J. Y., Koppelman, G. H., Postma, D. S., Pennell, C. E., Jarvelin, M.-R., Custovic, A., ... Bønnelykke, K. (2017). Shared genetic variants suggest common pathways in allergy and autoimmune diseases. Journal of Allergy and Clinical Immunology. Advance online publication. https://doi.org/10.1016/j.jaci.2016.10.055

@article{bfce23bb4c324d3395ecded425e488e1,

title = "Shared genetic variants suggest common pathways in allergy and autoimmune diseases",

abstract = "BackgroundThe relationship between allergy and autoimmune disorders is complex and poorly understood. ObjectiveTo investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms.MethodsWe meta-analyzed two GWAS on self-reported allergy and sensitization comprising a total of 62,330 individuals. These results were used to calculate enrichment for SNPs previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites, and characterized commonalities in the variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DHS data, and compared the allergy data with all known diseases. ResultsAmong 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (p=1.4e-17) encompassing 29 loci at a false discovery rate<0.05. Such enrichment seemed to be a general characteristic for all autoimmune diseases. Among the common loci, 48% had the same direction of effect for allergy and autoimmune diseases. Additionally, we observed an enrichment of allergy SNPs falling within immune pathways and regions of chromatin accessible in immune cells that was also represented in autoimmune diseases, but not in other diseases. ConclusionWe identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared diseases mechanisms. Further studies of these shared genetic mechanisms might help understanding the complex relationship between these diseases, including the parallel increase in disease prevalence. ",

keywords = "Allergy, Single Nucleotide Polymorphism, Autoimmune Disease, Autoimmunity, Genetic Association Studies",

author = "Eskil Kreiner-Moller and Johannes Waage and Marie Standl and Susanne Brix and Pers, {Tune H} and Alves, {Alexessander Couto} and Warrington, {Nicole M.} and Tiesler, {Carla M T} and Elaine Fuertes and Lude Franke and Hirschhorn, {Joel N} and Alan James and Angela Simpson and Tung, {Joyce Y} and Koppelman, {Gerard H} and Postma, {Dirkje S} and Pennell, {Craig E} and Marjo-Ritta Jarvelin and Adnan Custovic and Nicholas Timpson and Ferreira, {Manuel A} and Strachan, {David P} and John Henderson and Hinds, {David A} and Hans Bisgaard and Klaus B{\o}nnelykke",

year = "2017",

month = feb,

day = "8",

doi = "10.1016/j.jaci.2016.10.055",

language = "English",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

}

Kreiner-Moller, E, Waage, J, Standl, M, Brix, S, Pers, TH, Alves, AC, Warrington, NM, Tiesler, CMT, Fuertes, E, Franke, L, Hirschhorn, JN, James, A, Simpson, A, Tung, JY, Koppelman, GH, Postma, DS, Pennell, CE, Jarvelin, M-R, Custovic, A, Timpson, N, Ferreira, MA, Strachan, DP, Henderson, J, Hinds, DA, Bisgaard, H & Bønnelykke, K 2017, 'Shared genetic variants suggest common pathways in allergy and autoimmune diseases', Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2016.10.055

TY - JOUR

T1 - Shared genetic variants suggest common pathways in allergy and autoimmune diseases

AU - Kreiner-Moller, Eskil

AU - Waage, Johannes

AU - Standl, Marie

AU - Brix, Susanne

AU - Pers, Tune H

AU - Alves, Alexessander Couto

AU - Warrington, Nicole M.

AU - Tiesler, Carla M T

AU - Fuertes, Elaine

AU - Franke, Lude

AU - Hirschhorn, Joel N

AU - James, Alan

AU - Simpson, Angela

AU - Tung, Joyce Y

AU - Koppelman, Gerard H

AU - Postma, Dirkje S

AU - Pennell, Craig E

AU - Jarvelin, Marjo-Ritta

AU - Custovic, Adnan

AU - Timpson, Nicholas

AU - Ferreira, Manuel A

AU - Strachan, David P

AU - Henderson, John

AU - Hinds, David A

AU - Bisgaard, Hans

AU - Bønnelykke, Klaus

PY - 2017/2/8

Y1 - 2017/2/8

N2 - BackgroundThe relationship between allergy and autoimmune disorders is complex and poorly understood. ObjectiveTo investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms.MethodsWe meta-analyzed two GWAS on self-reported allergy and sensitization comprising a total of 62,330 individuals. These results were used to calculate enrichment for SNPs previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites, and characterized commonalities in the variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DHS data, and compared the allergy data with all known diseases. ResultsAmong 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (p=1.4e-17) encompassing 29 loci at a false discovery rate<0.05. Such enrichment seemed to be a general characteristic for all autoimmune diseases. Among the common loci, 48% had the same direction of effect for allergy and autoimmune diseases. Additionally, we observed an enrichment of allergy SNPs falling within immune pathways and regions of chromatin accessible in immune cells that was also represented in autoimmune diseases, but not in other diseases. ConclusionWe identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared diseases mechanisms. Further studies of these shared genetic mechanisms might help understanding the complex relationship between these diseases, including the parallel increase in disease prevalence.

AB - BackgroundThe relationship between allergy and autoimmune disorders is complex and poorly understood. ObjectiveTo investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms.MethodsWe meta-analyzed two GWAS on self-reported allergy and sensitization comprising a total of 62,330 individuals. These results were used to calculate enrichment for SNPs previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites, and characterized commonalities in the variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DHS data, and compared the allergy data with all known diseases. ResultsAmong 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (p=1.4e-17) encompassing 29 loci at a false discovery rate<0.05. Such enrichment seemed to be a general characteristic for all autoimmune diseases. Among the common loci, 48% had the same direction of effect for allergy and autoimmune diseases. Additionally, we observed an enrichment of allergy SNPs falling within immune pathways and regions of chromatin accessible in immune cells that was also represented in autoimmune diseases, but not in other diseases. ConclusionWe identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared diseases mechanisms. Further studies of these shared genetic mechanisms might help understanding the complex relationship between these diseases, including the parallel increase in disease prevalence.

KW - Allergy

KW - Single Nucleotide Polymorphism

KW - Autoimmune Disease

KW - Autoimmunity

KW - Genetic Association Studies

U2 - 10.1016/j.jaci.2016.10.055

DO - 10.1016/j.jaci.2016.10.055

M3 - Article (Academic Journal)

C2 - 28188724

SN - 0091-6749

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

ER -

Shared genetic variants suggest common pathways in allergy and autoimmune diseases

Abstract

Keywords

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Projects

MRC UoB UNITE Unit - programme 3

THE NATURAL HISTORY OF ASTHMA AND WHEEZING ILLNESSES FROM BIRTH TO ADOLESCENCE: DETERMINANTS OF THE REMISSION OF ASTHMA

EXTENSION OF RD1321 VIA IOP.

Cite this