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

Citations Over TimeTop 1% of 2015 papers

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.

Related Papers

• → Gene and pathway-based second-wave analysis of genome-wide association studies(2009)240 cited
• → The combination of a genome-wide association study of lymphocyte count and analysis of gene expression data reveals novel asthma candidate genes(2012)52 cited
• → Genome-wide association studies in aging-related processes such as diabetes mellitus, atherosclerosis and cancer(2007)43 cited
• → A genome-wide association study links small-vessel ischemic stroke to autophagy(2017)19 cited
• → GWAS summary-based pathway analysis correcting for the genetic confounding impact of environmental exposures(2017)4 cited