Shared genetic variants suggest common pathways in allergy and autoimmune diseases

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 - 2017/9

Y1 - 2017/9

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.jaci.2016.10.055

DO - 10.1016/j.jaci.2016.10.055

M3 - Journal article

C2 - 28188724

SN - 0091-6749

VL - 140

SP - 771

EP - 781

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 3

ER -