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Does hay fever have a genetic cause?

Do you suffer from hay fever? Do you dread the onset of warm spring weather almost as much as you look forward to it? If so, you are not alone as large numbers of people around the world are also sufferers. Have you ever wondered why you have hay fever, or whether you have inherited it? This article will try to answer this question, but first, let us take a general look at hay fever.

How many people suffer from hay fever?

In 2018, approximately 24 million people in the United States alone were diagnosed with this seasonal allergy [1]. In the UK, it is estimated that hay fever affects anywhere between 10 and 16 million people [2, 3]. The large European Community Respiratory Health survey, which included 48 centers in 22 countries, predominantly in Europe, but also in other countries including India, Australia and New Zealand, reported that nasal allergy and hay fever have a prevalence of 9.5% to 40.9% with a median value of 20.9% [4]. What is clear, even with the geographical differences, is that hay fever affects many people; it may even be under reported if people with only mild symptoms seek to manage their condition without visiting a medical professional.

What exactly is hay fever?

Hay fever is a type of allergy and one of the most common. It is an allergy to pollen, usually from trees and grasses, but also weed pollen. It is estimated that 150 million people in Europe alone suffer from an allergy and 10 million adults suffer from more than one [5].

Hay fever is also called seasonal allergic rhinitis as it occurs most often in spring and summer when pollen from trees and grasses is in the air. Pollen is an allergen, meaning that your immune system reacts to it causing an allergic reaction in your body. This results in inflammatory responses as well as generalized symptoms. Although allergic reactions can have many symptoms that include coughing and sneezing, rashes, sore throat, headache, or even breathing difficulties that can lead to death, in the case of hay fever, symptoms of the allergic reaction usually include:

  • itchy, red, watery eyes
  • sore or itchy throat
  • itchy mouth, nose or ears
  • runny or blocked nose
  • sneezing
  • coughing
  • headache
  • tiredness (fatigue)

How does this allergic reaction occur?

Sensitization or initial exposure

The first step in developing an allergy to something is sensitization. This is the initial exposure or first contact with the allergen (in this case pollen). The immune system begins to react by producing specific immunoglobulin E (IgE) antibodies capable of binding to the allergen, but there are no symptoms yet.

Subsequent exposure

Allergy symptoms occur when there is subsequent exposure to the allergen. For hay fever, symptoms occur soon (30-60 minutes) after exposure [6]. This is called immediate hypersensitivity and is mediated by IgE antibodies on the surface of mast cells, which are cells of the immune system. The allergen (pollen) binds to the IgE and activates the mast cells causing them to release inflammatory substances called mediators, which cause the symptoms. One of these mediators is called histamine.

Is hay fever inherited?

Unfortunately, this question does not have a simple answer. We can say that the tendency to have an allergy, such as hay fever, is inherited and that hay fever is known to have a genetic component. However, it is probable that the development of hay fever is also influenced by other factors, such as the environment and diet, and that the interactions between genetic risk factors and these factors are clearly complicated. It should also be pointed out that many studies in this field investigate the genetics of allergic rhinitis, which includes not only seasonal rhinitis but also perennial (non-seasonal) allergic rhinitis that may be caused by pet fur or dust.

Atopy

The inherited (genetic) tendency of an individual to develop an allergic disease such as asthma, allergic rhinitis or eczema is called atopy,andasthma, allergic rhinitis or eczema are called atopic diseases. A person with atopy has increased IgE production, and as we learnt above, IgE is responsible for the immune response that causes the symptoms, although not everyone with atopy develops an allergy [7].

The genetics of atopy is one avenue of allergy research. A genome wide association study of allergic sensitization from 2013 suggested 10 susceptibility genes for allergic sensitization: TLR6, C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1, LPP, MYC, IL2 and HLA-B, and estimated that they accounted for at least 25% of allergic sensitization and allergic rhinitis. Many of these genes are known to have roles in the immune system [8].

Genetic risk

Twin studies are useful to look at the effect of genetics versus environmental factors and to assess the influence of genetics on hay fever. One study reported that identical twins were more likely to both be sufferers of hay fever than non-identical twins were, a fact that immediately supports the role of genetics. It went on to say that, additive genetic effects accounted for 71% of the individual susceptibility to hay fever and non-shared environmental effects accounted for 29% [9]. Twin studies have also provided estimates for the heritability of hay fever. Heritability is the amount of variation that is due to genetics, and studies include ranges of 33-76% in a study of 7-9-year-old Swedish twins [10] and 74-82% in a Finnish study of 16‑year-old twins [11]. Although estimates of heritability vary considerably within and between studies, it is clear that hay fever has an associated genetic risk.

In 2018, researchers published a study that identified 41 risk genes that increase the risk of developing hay fever, including 20 that were previously unknown. The authors suggested that the genes are involved in various immune pathways and that amino acid variants are important for antigen binding [12].

Other risk factors

In addition to a family history of hay fever or the presence of asthma or eczema, other factors including environmental exposure to pet hair, mold, dust, or air pollution, may increase the risk of developing hay fever or perennial allergic rhinitis [13].

Hay fever and other allergies

10 million adults in Europe suffer from more than one allergy [5] and hay fever is known to occur with other allergies, especially asthma and eczema. People with asthma, in particular, are often likely to be hay fever sufferers and it has even been suggested that asthma and hay fever may represent two parts of the same disease spectrum affecting different body parts [14].

The genetic relationship between hay fever, asthma and eczema has been well studied and genetic links have been established. One study in 2018 found that asthma, hay fever and eczema share a large number (136) of genetic risk variants that dysregulate the expression of immune-related genes [15]. Indeed, the number of genes thought to be shared between these three conditions continues to increase, with a more recent study from 2020 reporting 150 shared risk genes, including 60 that were previously unknown [16]. While these two studies and others have helped to establish a genetic link between hay fever, asthma and eczema, they provide information about shared risk genes rather than elucidating a genetic cause.

Overlaps between risk genes for hay fever and risk genes for autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and inflammatory bowel disease have also been found [8, 17].

Is the number of people with hay fever increasing?

The number of people with an allergy has been increasing over the last 20-30 years [18, 19]. For example, a two- to three-fold increase in the number of people with allergic rhinitis (this can include non-seasonal allergies to allergens such as dust or pet fur) has been reported in the UK in the last 20 years [19].

Researchers do not believe that genetics alone can account for this increase. Indeed, the interaction of risk genes with environmental and lifestyle factors is suspected to be driving the increase [17].

Conclusions

Hay fever or allergic rhinitis is a common, widespread allergy with typical allergy symptoms. Although hay fever is known to have a genetic component and risk genes have been identified, it is highly likely that other factors such as environment and diet are just as important in its development. Research continues into the genetics of hay fever and the relationships between hay fever and other atopic diseases in the hope that one day an understanding of what causes hay fever will open up new treatment solutions for sufferers.

References

[1] CDC Centers for Disease Control and Prevention. Allergies and Hay Fever. Retrieved 29 June 2020 from https://www.cdc.gov/nchs/fastats/allergies.htm

[2] The Met Office. Surviving hay fever: A guide for sufferers. Retrieved 29 June 2020 from https://www.metoffice.gov.uk/weather/warnings-and-advice/seasonal-advice/health-wellbeing/pollen/surviving-hay-fever

[3] National Allergy Research Foundation retrieved 29 June 2020 from https://www.narf.org.uk/the-allergy-explosion

[4] Janson C et al. The European Community Respiratory Health Survey: what are the main results so far? European Community Respiratory Health Survey II. Eur Respir J 2001 18(3):598-611. doi: 10.1183/09031936.01.00205801. PMID: 11589359. https://erj.ersjournals.com/content/18/3/598.long

[5] EEACI patients. Retrieved 7 July 2020 from https://patients.eaaci.org/

[6] EEACI patients. What is an allergy? Retrieved 7 July 2020 from https://patients.eaaci.org/what-is-allergy/

[7] Jarvis D and Burney P. ABC of allergies. The epidemiology of allergic disease. BMJ. 1998 Feb 21;316(7131):607-10. doi: 10.1136/bmj.316.7131.607. Erratum in: BMJ 1998 Apr 4;316(7137):1078. PMID: 9518918; PMCID: PMC1112638. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1112638/pdf/607.pdf

[8] Bønnelykke K et al. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. Nat Genet 2013 45(8):902-906. doi: 10.1038/ng.2694. Epub 2013 Jun 30. PMID: 23817571; PMCID: PMC4922420. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922420/

[9] Thomsen SF et al. Genetic and environmental contributions to hay fever among young adult twins. Respir Med 2006 100(12): 2177-2182. doi: 10.1016/j.rmed.2006.03.013. Epub 2006 May 2. PMID: 16650971. https://doi.org/10.1016/j.rmed.2006.03.013

[10] Lichtenstein P and Svartengren M. Genes, environments, and sex: factors of importance in atopic diseases in 7‑9‑year-old Swedish twins. Allergy 1997 52(11):1079-86. doi: 10.1111/j.1398-9995.1997.tb00179.x. PMID: 9404559. https://doi.org/10.1111/j.1398-9995.1997.tb00179.x

[11] Räsänen M et al. Hay fever–a Finnish nationwide study of adolescent twins and their parents. Allergy 1998 53(9):885-90. doi: 10.1111/j.1398-9995.1998.tb03996.x. PMID: 9788691. https://doi.org/10.1111/j.1398-9995.1998.tb03996.x

[12] Waage, J et al. Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis. Nat Genet 2018 50(8):1072–1080. doi: 10.1038/s41588-018-0157-1. Epub 2018 Jul 16. PMID: 30013184 https://doi.org/10.1038/s41588-018-0157-1

[13] Wang DY. Risk factors of allergic rhinitis: genetic or environmental? Ther Clin Risk Manag 2005 1(2):115-23. doi: 10.2147/tcrm.1.2.115.62907. PMID: 18360551; PMCID: PMC1661616. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1661616/

[14] Ober C and Yao TC. The genetics of asthma and allergic disease: a 21st century perspective. Immunol Rev 2011 242(1):10-30. doi: 10.1111/j.1600-065X.2011.01029.x. PMID: 21682736; PMCID: PMC3151648. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151648/

[15] Ferreira MA et al. Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology. Nat Genet 2017 49(12):1752-1757. doi: 10.1038/ng.3985. Epub 2017 Oct 30. PMID: 29083406; PMCID: PMC5989923. https://pubmed.ncbi.nlm.nih.gov/29083406/

[16] Guo H et al (2020) Identifying shared risk genes for asthma, hay fever, and eczema by multi-trait and multiomic association analyses. Front Genet 11:270. doi: 10.3389/fgene.2020.00270. PMID: 32373153; PMCID: PMC7176997. https://doi.org/10.3389/fgene.2020.00270

[17] Eurekalert. Major study identifies new hay fever risk genes. Retrieved 14 July 2022 from https://www.eurekalert.org/news-releases/683899

[18] Natasha Allergy Research Foundation. Why are allergies on the rise? Retrieved 7 July 2020 from https://www.narf.org.uk/the-allergy-explosion

[19] Lee TH. Allergy: the unmet need. Clin Med (Lond). 2003 3(4):303-5. doi: 10.7861/clinmedicine.3-4-303. PMID: 12938740; PMCID: PMC5351939. https://www.rcpjournals.org/content/clinmedicine/3/4/303

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