Researchers explored the genetics of hay fever in a recent meta-analysis published in Nature Genetics.
Allergic rhinitis, more commonly known as hay fever, is an allergic response triggered by airborne allergens such as dust or pollen. Those who suffer from these allergies typically experience nasal inflammation, sneezing, nasal congestion, itchy, watery eyes, and a runny nose seasonally or year-round. Studies have identified several genes associated with hay fever but largely have not been implicated across studies. An improved understanding of the genes and related mechanisms could lead to improved forms of treatment and management.
In a recent meta-analysis published in Nature Genetics, researchers explored the genetics of hay fever to better understand the mechanisms that underlie the condition. They collected data from genome-wide association studies (GWAS) examining the risk associated with various genes or specific forms of genes alone or in combination. Across the studies, patient and genetic data were collected from 59,762 individuals with the allergies and 152,358 without.
Forty-one genes were found to be highly associated with hay fever – 40 of the 41 genes were found to increase risk, and one was found to decrease risk. As expected, many of the genes implicated are known to play roles in allergic reactions and the function of the immune system. In particular, variants of a number of MHC class II genes – important for the recognition by certain white blood cells of many parasites and allergens and the subsequent generation of immune responses to them – were implicated, suggesting hay fever is associated with changes in the allergen-recognizing regions of MHC class II proteins.
Hay fever often presents alongside other conditions including allergic sensitization, non-allergic rhinitis, asthma, and eczema. In particular, allergic sensitization – in which the immune system generates IgE antibodies in response to allergens – is thought to be a precursor to hay fever and non-allergic rhinitis is defined as having the symptoms without evidence of allergic sensitization.
To distinguish the genetics of hay fever from these other conditions, the researchers first identified the genes in GWAS studies examining allergic sensitization to airborne allergens and non-allergic rhinitis were compared to those associated with hay fever. Significant overlap was found between the genes related to the biological processes behind allergic sensitization and to hay fever. However, allergic sensitization was associated with gene activity in a wider array of immune cells than hay fever.
Hay fever was most strongly associated with gene activity in B cells and T2 Helper cells – white blood cells commonly involved in immune reactions to parasite and allergens. Secondly, the genetic similarity between allergic sensitization, asthma, and eczema were compared to hay fever. The strongest associations with hay fever were found for allergic sensitization and the weakest were found for eczema. Of the 41 genes strongly associated with hay fever, 28 were also associated with allergic sensitization.
The study findings suggest genetic pathways and biological processes are shared between hay fever and allergic sensitization, though differences in gene activity in certain immune cells were found between the conditions. Future research will be required to explore these mechanisms in depth and determine a causal relationship between allergic sensitization and hay fever.
Written by Raishard Haynes, MBS
Reference: Waage, J. et al. (2018). Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis. Nat. Genet. https://doi.org/10.1038/s41588-018-0157-1
