Abstract
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. To identify genetic variants associated with challenge-proven peanut allergy. We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all~1year 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. We identified 21 independent associations at P≤5×10-5 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=2×10-4 ). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population. Genetic determinants for challenge-proven peanut allergy include alleles at the HLA-DRB1 locus.
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