Shared genetic variants suggest common pathways in allergy and autoimmune diseases
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Shared genetic variants suggest common pathways in allergy and autoimmune diseases. / Kreiner, Eskil; Waage, Johannes; Standl, Marie; Brix, Susanne; Pers, Tune H; Couto Alves, Alexessander; Warrington, Nicole M; Tiesler, Carla Mt; Fuertes, Elaine; Franke, Lude; Hirschhorn, Joel N; James, Alan; Simpson, Angela; Tung, Joyce Y; Koppelman, Gerard H; Postma, Dirkje S; Pennell, Craig E; Jarvelin, Marjo-Riitta; Custovic, Adnan; Timpson, Nicholas; Ferreira, Manuel A; Strachan, David P; Henderson, John; Hinds, David; Bisgaard, Hans; Bønnelykke, Klaus.
I: The Journal of allergy and clinical immunology, Bind 140, Nr. 3, 2017, s. 771-781.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Shared genetic variants suggest common pathways in allergy and autoimmune diseases
AU - Kreiner, Eskil
AU - Waage, Johannes
AU - Standl, Marie
AU - Brix, Susanne
AU - Pers, Tune H
AU - Couto Alves, Alexessander
AU - Warrington, Nicole M
AU - Tiesler, Carla Mt
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-Riitta
AU - Custovic, Adnan
AU - Timpson, Nicholas
AU - Ferreira, Manuel A
AU - Strachan, David P
AU - Henderson, John
AU - Hinds, David
AU - Bisgaard, Hans
AU - Bønnelykke, Klaus
N1 - Copyright © 2017. Published by Elsevier Inc.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.jaci.2016.10.055
DO - 10.1016/j.jaci.2016.10.055
M3 - Journal article
C2 - 28188724
VL - 140
SP - 771
EP - 781
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
ER -
ID: 174400961