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

Kreiner, E; Waage, J; Standl, M; Brix, S; Pers, TH; Couto Alves, A; Warrington, NM; Tiesler, CM; Fuertes, E; Franke, L; et al. 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, M-R; Custovic, A; Timpson, N; Ferreira, MA; Strachan, DP; Henderson, J; Hinds, D; Bisgaard, H; Bønnelykke, K (2017) Shared genetic variants suggest common pathways in allergy and autoimmune diseases. J Allergy Clin Immunol, 140 (3). pp. 771-781. ISSN 1097-6825 https://doi.org/10.1016/j.jaci.2016.10.055
SGUL Authors: Strachan, David Peter

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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.

Item Type: Article
Additional Information: © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Allergy, Autoimmune Disease, Autoimmunity, Genetic Association Studies, Single Nucleotide Polymorphism, Allergy, 1107 Immunology
SGUL Research Institute / Research Centre: Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: J Allergy Clin Immunol
ISSN: 1097-6825
Language: eng
Dates:
DateEvent
September 2017Published
8 February 2017Published Online
11 October 2016Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
PubMed ID: 28188724
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/108385
Publisher's version: https://doi.org/10.1016/j.jaci.2016.10.055

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