title: Shared genetic variants suggest common pathways in allergy and autoimmune diseases.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Eskil
authors.initials: E
authors.lastname: Kreiner
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Johannes
authors.initials: J
authors.lastname: Waage
authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Standl
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Brix
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Mass; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Mass; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Tune H
authors.initials: TH
authors.lastname: Pers
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Alexessander
authors.initials: A
authors.lastname: Couto Alves
authors.affiliation: University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia; School of Women's and Infants' Health, University of Western Australia, Perth, Australia.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Warrington
authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Ludwig-Maximilians-Universität of Munich, Dr. von Hauner Children's Hospital, Munich, Germany.
authors.forename: Carla M T
authors.initials: CMT
authors.lastname: Tiesler
authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuertes
authors.affiliation: Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Lude
authors.initials: L
authors.lastname: Franke
authors.affiliation: Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Mass; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Mass; Department of Genetics, Harvard Medical School, Boston, Mass.
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.affiliation: Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Australia; School of Medicine and Pharmacology, University of West Australia, Nedlands, Australia; Department of Pulmonary Physiology, West Australian Sleep Disorders Research Institute, Nedlands, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: James
authors.affiliation: University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Simpson
authors.affiliation: 23andMe, Mountain View, Calif.
authors.forename: Joyce Y
authors.initials: JY
authors.lastname: Tung
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC Research Institute, Groningen, The Netherlands.
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Koppelman
authors.affiliation: University of Groningen, University Medical Center Groningen, Department Pulmonary Medicine and Tuberculosis, GRIAC Research Institute, Groningen, The Netherlands.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: School of Women's and Infants' Health, University of Western Australia, Perth, Australia.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Pennell
authors.affiliation: Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom; Center for Life Course Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; Unit of Primary Care, Oulu University Hospital, Oulu, Finland; Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland.
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Jarvelin
authors.affiliation: University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Adnan
authors.initials: A
authors.lastname: Custovic
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Timpson
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Ferreira
authors.affiliation: Population Health Research Institute, St George's, University of London, London, United Kingdom.
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Henderson
authors.affiliation: 23andMe, Mountain View, Calif.
authors.forename: David
authors.initials: D
authors.lastname: Hinds
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: bisgaard@copsac.com.
authors.forename: Hans
authors.initials: H
authors.lastname: Bisgaard
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bønnelykke
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
keywords: Allergy; autoimmune disease; autoimmunity; genetic association studies; single nucleotide polymorphism