杭州浙大迪迅生物基因工程有限公司Release date：2019-01-17
JACI：
September 2017Volume 140, Issue 3, Pages 771–781
DOI: https://doi.org/10.1016/j.jaci.2016.10.055
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.
All Author:
Eskil Kreiner, MD, PhD?, Johannes Waage, PhD?, Marie Standl, PhD, Susanne Brix, PhD, Tune H. Pers, PhD, Alexessander Couto Alves, PhD, Nicole M. Warrington, PhD, Carla M.T. Tiesler, MSc, Elaine Fuertes, PhD, Lude Franke, PhD, Joel N. Hirschhorn, MD, PhD, Alan James, MD, Angela Simpson, MD, PhD, Joyce Y. Tung, PhD, Gerard H. Koppelman, MD, PhD, Dirkje S. Postma, MD, PhD, Craig E. Pennell, MD, PhD, Marjo-Riitta Jarvelin, MD, Adnan Custovic, MD, PhD, Nicholas Timpson, PhD, Manuel A. Ferreira, PhD, David P. Strachan, MD, John Henderson, MD, David Hinds, PhD, Hans Bisgaard, MD, DMSc'Correspondence information about the author MD, DMSc Hans Bisgaard Email the author MD, DMSc Hans Bisgaard, Klaus B?nnelykke, MD, PhD
[IF:13.1]
Shared genetic variants suggest common pathways in allergy and autoimmune diseasesSeptember 2017Volume 140, Issue 3, Pages 771–781
DOI: https://doi.org/10.1016/j.jaci.2016.10.055
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.
All Author:
Eskil Kreiner, MD, PhD?, Johannes Waage, PhD?, Marie Standl, PhD, Susanne Brix, PhD, Tune H. Pers, PhD, Alexessander Couto Alves, PhD, Nicole M. Warrington, PhD, Carla M.T. Tiesler, MSc, Elaine Fuertes, PhD, Lude Franke, PhD, Joel N. Hirschhorn, MD, PhD, Alan James, MD, Angela Simpson, MD, PhD, Joyce Y. Tung, PhD, Gerard H. Koppelman, MD, PhD, Dirkje S. Postma, MD, PhD, Craig E. Pennell, MD, PhD, Marjo-Riitta Jarvelin, MD, Adnan Custovic, MD, PhD, Nicholas Timpson, PhD, Manuel A. Ferreira, PhD, David P. Strachan, MD, John Henderson, MD, David Hinds, PhD, Hans Bisgaard, MD, DMSc'Correspondence information about the author MD, DMSc Hans Bisgaard Email the author MD, DMSc Hans Bisgaard, Klaus B?nnelykke, MD, PhD
2019-1-10 Article
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