Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA ‐ DRB 1

• Published in: Clinical and experimental allergy Vol. 47; no. 2; pp. 217 - 223
• Main Authors: Martino, D. J., Ashley, S., Koplin, J., Ellis, J., Saffery, R., Dharmage, S. C., Gurrin, L., Matheson, M. C., Kalb, B., Marenholz, I., Beyer, K., Lee, Y.‐A., Hong, X., Wang, X., Vukcevic, D., Motyer, A., Leslie, S., Allen, K. J., Ferreira, M. A. R.
• Format: Journal Article
• Language: English
• Published: 01.02.2017
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/cea.12863

Summary 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 −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 ‐ DRB 1 ( P  =   2 × 10 −4 ). Our study therefore reproduced previous findings for the association between peanut allergy and HLA ‐ DRB 1 in this Australian population. Conclusions and Clinical Relevance Genetic determinants for challenge‐proven peanut allergy include alleles at the HLA ‐ DRB 1 locus.