Shared genetic variants suggest common pathways in allergy and autoimmune diseases

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:140

Article

Kreiner, Eskil¹  Waage, Johannes¹  Standl, Marie²  Brix, Susanne³  Pers, Tune H.^4,5,6,30  Alves, Alexessander Couto⁷  Warrington, Nicole M.^8,9,10  Tiesler, Carla M. T.^2,11  Fuertes, Elaine²  Franke, Lude¹²  Hirschhorn, Joel N.^4,5,6,13  James, Alan^14,15,16  Tung, Joyce Y.¹⁸  Koppelman, Gerard H.¹⁹  Postma, Dirkje S.²⁰  Pennell, Craig E.¹⁰  Jarvelin, Marjo-Riitta^{21,22,23,24,25}  Custovic, Adnan¹⁷  Timpson, Nicholas²⁶  Ferreira, Manuel A.²⁸  Strachan, David P.²⁹  Henderson, John²⁷  Hinds, David¹⁸  Bisgaard, Hans¹  Bonnelykke, Klaus¹ 

[1] Univ Copenhagen, Copenhagen Prospect Studies Asthma Childhood, COPSAC, Copenhagen, Denmark

[2] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany

[3] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

[4] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA

[5] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA

[6] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA USA

[7] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England

[8] Univ Queensland, Brisbane, Qld 4072, Australia

[9] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4072, Australia

[10] Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA, Australia

[11] Ludwig Maximilians Univ Munchen, Dr Van Hauner Childrens Hosp, Munich, Germany

[12] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[13] Harvard Med Sch, Dept Genet, Boston, MA USA

[14] Sir Charles Gairdner Hosp, Busselton Populat Med Res Fdn, Perth, WA, Australia

[15] Univ West Australia, Sch Med & Pharmacol, Nedlands, WA, Australia

[16] West Australian Sleep Disorders Res Inst, Dept Pulm Physiol, Nedlands, WA, Australia

[17] Univ Manchester, Manchester Acad Hlth Sci Ctr, Univ Hosp South Manchester, NHS Fdn Trust, Manchester, Lancs, England

[18] 23andMe, Mountain View, CA USA

[19] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat Pulmonol & Pediat Allergol, Beatrix Childrens Hosp,GRIAC Res Inst, Groningen, Netherlands

[20] Univ Groningen, Univ Med Ctr Groningen, Dept Pulm Med & TB, GRIAC Res Inst, Groningen, Netherlands

[21] Imperial Coll London, Sch Publ Hlth, Ctr Environm & Hlth, MRC,Hlth Protect Agcy HPA,Dept Epidemiol & Biosta, London, England

[22] Ctr Life Course Epidemiol, Fac Med, Oulu, Finland

[23] Univ Oulu, Bioctr Oulu, Oulu, Finland

[24] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland

[25] Natl Inst Hlth & Welf, Dept Children & Young People & Families, Oulu, Finland

[26] MRC Integrat Epidemiol Unit, Bristol, Avon, England

[27] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England

[28] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[29] St Georges Univ London, Populat Hlth Res Inst, London, England

[30] Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark

关键词: Allergy;    single nucleotide polymorphism;    autoimmune disease;    autoimmunity;    genetic association studies;   

DOI  :  10.1016/j.jaci.2016.10.055

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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