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GWAS Yields Risk Variants, Methylation Profiles Associated with Peanut Allergy

NEW YORK (GenomeWeb) – In Nature Communications today, an international team led by investigators at Johns Hopkins University described both genetic variants and epigenetic shifts associated with peanut allergy in individuals of European descent.

Using samples collected for the Chicago Food Allergy Study, the researchers genotyped more than 1,300 children with one of nine different food allergies, along with one or both of their biological parents.

In the case of peanut allergy, they detected risk loci falling in and around the human leukocyte antigen (HLA) regions HLA-DR and HLA-DQ regions — results they replicated with the help of samples from additional individuals of European descent.

When the team took a closer look at the peanut allergy-linked loci, it found that they tended to correspond with peanut allergy-related epigenetic profiles, including altered methylation at genes such as HLA-DRB1 and HLA-DQB1.

The study's senior author Xiaobin Wang argued that the results may pave the way for new strategies to treat or prevent peanut and other food allergies. Wang is director of the Johns Hopkins Bloomberg School of Public Health's Center on the Early Life Origins of Disease.

"We might be able to use pharmaceutical treatment," Wang said in a statement, "but if we can figure out whether a lifestyle, nutrition[al], or environmental change could reduce allergies, that would be even better."

Food allergies typically involve immune reactions to food proteins that are mediated by immunoglobulin E, the study's authors explained. Once rare, the incidence of food allergy has risen in the US in the past few decades and now affect between 2 and 10 percent of American children.

Such allergies affect everything from individuals' and families' quality of life to costs incurred to the health system, they noted, prompting interest in a more complete understanding of the factors behind them.

"A major obstacle to effective prevention and treatment of [food allergy] is our limited understanding of its causes and underlying biological mechanisms," the study's authors wrote.

In an effort to add to findings from past candidate gene studies — while providing a peek at possible epigenetic contributors — the researchers performed a three-stage GWAS involving 1,314 children with peanut, egg white, cow milk, soy, walnut, wheat, fish, shellfish, or sesame seed allergies and 1,444 of their parents.

The team successfully tested samples from 1,283 of the children and 1,411 parents using the Illumina HumanOmni 1-Quad beadchip. It then used imputed and directly genotyped SNPs in these samples to look for genetic associations with any food allergy, or with milk, egg, or peanut allergies in particular. 

After identifying apparent associations between peanut allergy risk in Europeans and loci near HLA-DQ and HLA-DRA genes on chromosome 6, the researchers verified these results through replication testing and meta-analyses that included data for dozens more European or non-European individuals with or without peanut allergies. 

Finally, the team folded in array-based DNA methylation profiles, comparing those found in individuals with peanut allergy, without peanut allergy, or with unknown allergy phenotypes.

That search led to differentially methylated sites at four genes, including regions showing methylation shifts depending on the presence or absence of the newly detected genetic risk variants for peanut allergy — results that may partly explain the variable peanut allergy penetrance found for those carrying the HLA variants.