Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children

Nat Commun. 2015 Feb 24;6:6304. doi: 10.1038/ncomms7304.

Abstract

Food allergy (FA) affects 2%-10% of US children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk and egg) in 2,759 US participants (1,315 children and 1,444 parents) from the Chicago Food Allergy Study, and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (P=5.5 × 10(-8)) and rs9275596 (P=6.8 × 10(-10)), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (P<5 × 10(-8)), and differential DNA methylation of the HLA-DQB1 and HLA-DRB1 genes partially mediate the identified SNP-PA associations. This study suggests that the HLA-DR and -DQ gene region probably poses significant genetic risk for PA.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • DNA Methylation
  • Epigenesis, Genetic
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • HLA-DQ Antigens / genetics*
  • HLA-DR Antigens / genetics*
  • Humans
  • Infant
  • Male
  • Peanut Hypersensitivity / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • United States
  • Young Adult

Substances

  • HLA-DQ Antigens
  • HLA-DR Antigens