title: Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1.
abstract: BACKGROUND
  Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genomewide association study (GWAS) has been published.
  
  
  OBJECTIVE
  To identify genetic variants associated with challenge-proven peanut allergy.
  
  
  METHODS
  We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphisms, as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts.
  
  
  RESULTS
  We identified 21 independent associations at P ≤ 5 × 10-5but were unable to replicate these. The most significant HLA association was the previously reported amino acid variant located at position 71, within the peptide-binding groove of HLA-DRB1 (P = 2 × 10-4). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population.
  
  
  CONCLUSIONS
  Genetic determinants for challenge-proven peanut allergy include alleles at the HLA-DRB1 locus.
authors.affiliation: Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: D J
authors.initials: DJ
authors.lastname: Martino
authors.affiliation: Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Melbourne, Vic., Australia.|Hudson Institute of Medical Research, Clayton, Vic., Australia.
authors.forename: S
authors.initials: S
authors.lastname: Ashley
authors.affiliation: Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Melbourne, Vic., Australia.|School of Population and Global Health, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: J
authors.initials: J
authors.lastname: Koplin
authors.affiliation: Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: J
authors.initials: J
authors.lastname: Ellis
authors.affiliation: Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: R
authors.initials: R
authors.lastname: Saffery
authors.affiliation: School of Population and Global Health, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: S C
authors.initials: SC
authors.lastname: Dharmage
authors.affiliation: School of Population and Global Health, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: L
authors.initials: L
authors.lastname: Gurrin
authors.affiliation: School of Population and Global Health, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: M C
authors.initials: MC
authors.lastname: Matheson
authors.affiliation: Pediatric Pneumology and Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.|Clinic for Pediatric Allergy, Experimental and Clinical Research Center of MDC, Charité, Berlin, Germany.|Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kalb
authors.affiliation: Clinic for Pediatric Allergy, Experimental and Clinical Research Center of MDC, Charité, Berlin, Germany.|Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Marenholz
authors.affiliation: Pediatric Pneumology and Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Beyer
authors.affiliation: Clinic for Pediatric Allergy, Experimental and Clinical Research Center of MDC, Charité, Berlin, Germany.|Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany.
authors.forename: Y-A
authors.initials: YA
authors.lastname: Lee
authors.affiliation: Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: X
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Melbourne, Vic., Australia.|Centre for Systems Genomics, Schools of Mathematics and Statistics and Biosciences, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: D
authors.initials: D
authors.lastname: Vukcevic
authors.affiliation: Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Melbourne, Vic., Australia.|Centre for Systems Genomics, Schools of Mathematics and Statistics and Biosciences, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: A
authors.initials: A
authors.lastname: Motyer
authors.affiliation: Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Melbourne, Vic., Australia.|Centre for Systems Genomics, Schools of Mathematics and Statistics and Biosciences, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: S
authors.initials: S
authors.lastname: Leslie
authors.affiliation: Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: K J
authors.initials: KJ
authors.lastname: Allen
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.
authors.forename: M A R
authors.initials: MA
authors.lastname: Ferreira
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016017:Odds Ratio; D021183:Peanut Hypersensitivity / Q000235:genetics* / Q000276:immunology*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D059811:HLA-DRB1 Chains
keywords: 
  GWAS
  ; food allergy; genetics; hypersensitivity; peanut allergy