Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1


  • D.J. Martino
  • S. Ashley
  • J. Koplin
  • J. Ellis
  • R. Saffery
  • S.C. Dharmage
  • L. Gurrin
  • M.C. Matheson
  • B. Kalb
  • I. Marenholz
  • K. Beyer
  • Y.A. Lee
  • X. Hong
  • X. Wang
  • D. Vukevic
  • A. Motyer
  • S. Leslie
  • K.J. Allen
  • M.A.R. Ferreira


  • Clinical and Experimental Allergy


  • Clin Exp Allergy 47 (2): 217-223


  • 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 x 10-5 but 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 x 10-4 ). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population. CONCLUSIONS AND CLINICAL RELEVANCE: Genetic determinants for challenge-proven peanut allergy include alleles at the HLA-DRB1 locus.