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Kreiner, E.* ; Waage, J.* ; Standl, M. ; Brix, S.* ; Pers, T.H.* ; Couto Alves, A.* ; Warrington, N.M.* ; Tiesler, C.M. ; 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.* ; Timpson, N.* ; Ferreira, M.A.* ; Strachan, D.P.* ; Henderson, J.* ; Hinds, D.A.* ; Bisgaard, H.* ; Bønnelykke, K.*

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

J. Allergy Clin. Immunol. 140, 771-781 (2017)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Allergy ; Autoimmune Disease ; Autoimmunity ; Genetic Association Studies ; Single Nucleotide Polymorphism; 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
ISSN (print) / ISBN 0091-6749
e-ISSN 1097-6825
Journal The journal of allergy and clinical immunology
Quellenangaben Volume: 140, Issue: 3, Pages: 771-781 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)