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Allergy GWAS Points to Asthma, Hay Fever, Eczema Overlap

NEW YORK (GenomeWeb) – An international team has identified overlapping genetic contributors for a handful of allergic conditions – asthma, hay fever, and eczema – that sometimes co-occur in the same individuals.

As they reported online today in Nature Genetics, the researchers did a genome-wide association study involving almost 361,000 individuals with or without allergic disease. Their search led to more than 100 allergy-associated variants in and around 132 genes, though only half a dozen of the variants showed ties to a specific allergic condition.

"With a few exceptions, the variants identified had similar effects on the individual disease entities. The risk variants, and their likely target genes, are predicted to influence overwhelmingly the function of immune cells," corresponding author Manuel Ferreira, a genetics and computational biology researcher at QIMR Berghofer Medical Research Institute, and his colleagues wrote.

From these and other findings, the team argued that much of the heritability of asthma, hay fever, and eczema may be shared, perhaps mediated in part by interacting cytosine methylation marks. For example, past research has uncovered expression-influencing methylation marks near at least 36 of the allergy-associated genes found so far.

"This observation raises the possibility that environmental effects on the methylation state of these CpGs might influence target gene expression and, by extension, allergic disease risk," the authors wrote, noting that "well-powered studies that address this possibility are warranted."

For their study, the researchers compared genotyping profiles at more than 8.3 million SNPs in 180,129 individuals of European ancestry for one or more of the allergic conditions considered and 180,709 individuals without, narrowing in on 136 allergy-associated variants at 99 loci. The set included variants implicated in asthma, hay fever, and/or eczema in the past, along with 73 SNPs not implicated in the conditions in the past.

When the team focused on 12,268 individuals with asthma alone, the 33,305 individuals who only had hay fever, and the 6,276 eczema-specific cases, it saw just six variants that were associated with only one allergic disease. Meanwhile, more than two-dozen variants had apparent ties to age of allergy disease onset.

The researchers estimated that the risky allergic disease variant set explained roughly 3 percent of inherited asthma risk, just shy of 4 percent of hay fever heritability, and just over 1 percent of the heritability for eczema. With the help of tissue-specific expression insights from the GTEx and ENCODE project, they narrowed in on genes and cell types suspected of influencing allergy risk.

The team's results suggest allergic disease-associated variants tend to impact immune functions involving lymphocyte cells such as natural killer cells, helper T cells, and certain B cells. Across the set of genes suspected to influence allergic disease, the group noted that at least 29 genes were previously proposed as drug targets for allergic or other conditions.