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Shared genetic variants suggest common pathways in allergy and autoimmune diseases.

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Title: Shared genetic variants suggest common pathways in allergy and autoimmune diseases.
Authors: Kreiner, E
Waage, J
Standl, M
Brix, S
Pers, TH
Couto Alves, A
Warrington, NM
Tiesler, CM
Fuertes, E
Franke, L
Hirschhorn, JN
James, A
Simpson, A
Tung, JY
Koppelman, GH
Postma, DS
Pennell, CE
Jarvelin, MR
Custovic, A
Timpson, N
Ferreira, MA
Strachan, DP
Henderson, J
Hinds, D
Bisgaard, H
Bønnelykke, K
Item Type: Journal Article
Abstract: BACKGROUND: The relationship between allergy and autoimmune disorders is complex and poorly understood. OBJECTIVE: We sought to investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. METHODS: We meta-analyzed 2 genome-wide association studies on self-reported allergy and sensitization comprising a total of 62,330 subjects. These results were used to calculate enrichment for single nucleotide polymorphisms (SNPs) previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites and characterized commonalities in 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 DNase-hypersensitive site data. Finally, we compared the allergy data with those of 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 of less than 0.05. Such enrichment seemed to be a general characteristic for 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 patients with autoimmune diseases but not those with other diseases. CONCLUSION: We identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared disease mechanisms. Further studies of these shared genetic mechanisms might help in understanding the complex relationship between these diseases, including the parallel increase in disease prevalence.
Issue Date: 8-Feb-2017
Date of Acceptance: 11-Oct-2016
URI: http://hdl.handle.net/10044/1/45543
DOI: https://dx.doi.org/10.1016/j.jaci.2016.10.055
ISSN: 1097-6825
Publisher: Elsevier
Start Page: 771
End Page: 781
Journal / Book Title: Journal of Allergy and Clinical Immunology
Volume: 140
Issue: 3
Copyright Statement: © 2017 American Academy of Allergy, Asthma & Immunology. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MR/K002449/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Allergy
Immunology
single nucleotide polymorphism
autoimmune disease
autoimmunity
genetic association studies
GENOME-WIDE ASSOCIATION
NF-KAPPA-B
CD4 T-CELLS
SUSCEPTIBILITY LOCI
RHEUMATOID-ARTHRITIS
1,25-DIHYDROXYVITAMIN D-3
MULTIPLE-SCLEROSIS
IMMUNE-RESPONSES
RISK LOCI
HAY-FEVER
Allergy
autoimmune disease
autoimmunity
genetic association studies
single nucleotide polymorphism
Autoimmune Diseases
Genome-Wide Association Study
Humans
Hypersensitivity
Polymorphism, Single Nucleotide
Humans
Autoimmune Diseases
Hypersensitivity
Polymorphism, Single Nucleotide
Genome-Wide Association Study
1107 Immunology
Allergy
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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