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

Xiumei Hong, Ke Hao, Christine Ladd-Acosta, Kasper D. Hansen, Hui Ju Tsai, Xin Liu, Xin Xu, Timothy A. Thornton, Deanna Caruso, Corinne A. Keet, Yifei Sun, Guoying Wang, Wei Luo, Rajesh Kumar, Ramsay Fuleihan, Anne Marie Singh, Jennifer S. Kim, Rachel E. Story, Ruchi S. Gupta, Peisong GaoZhu Chen, Sheila O. Walker, Tami R. Bartell, Terri H. Beaty, M. Daniele Fallin, Robert Schleimer, Patrick G. Holt, Kari Christine Nadeau, Robert A. Wood, Jacqueline A. Pongracic, Daniel E. Weeks, Xiaobin Wang

Research output: Contribution to journalArticlepeer-review

131 Scopus citations


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.

Original languageEnglish (US)
Article number6304
JournalNature communications
StatePublished - Mar 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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