Allergic diseases have become a significant health concern worldwide, with increasing prevalence and complexity.

A profound understanding of the genetic factors influencing allergies has advanced significantly, shedding light on why certain individuals develop hypersensitive immune responses to otherwise harmless substances.

Genetic Predisposition to Allergies

Genetic factors play a significant role in the development of allergic disease — what is passed on is the susceptibility to allergy, rather than a guarantee of a specific allergic reaction. For example, lay‑education sources indicate that if one parent has allergies the child’s chance of developing an allergy rises to around 30–50 %, and if both parents are allergic it may rise to around 60–80 %. Clinical studies support the trend that two or more allergic family members meaningfully increase risk compared to none, though the exact percentage varies by allergy type and environmental context.

Current genetic investigations have identified numerous genes associated with predispositions to asthma, allergic rhinitis (hay fever), and atopic dermatitis (eczema). For example, asthma exhibits a wide genetic influence ranging from 35 to 95%, while atopic dermatitis shows a genetic contribution of about 70 to 85%. These variations underscore that genetics substantially affect the onset and severity of allergic diseases but interact dynamically with environmental factors to influence clinical outcomes.

Insights from Twin and Family Studies

Twin studies have been instrumental in quantifying genetic contributions to allergy development. Monozygotic twins, who share nearly identical genetic material, display significantly higher concordance rates for atopy compared to dizygotic twins. Furthermore, research indicates that the age of allergy onset often occurs earlier when the mother has a history of allergic disease, suggesting possible maternal genetic or epigenetic influences beyond simple inheritance.

Linkage analyses have revealed genomic regions linked to allergic diseases, including chromosomal loci bearing genes responsible for IgE receptor expression, central to allergic immune responses. However, studies regarding maternal versus paternal genetic influence remain inconclusive, with some indicating stronger maternal effects and others suggesting paternal genetic contributions.

Molecular Mechanisms and Gene Variants

Genetic studies have shown that the majority of variants associated with allergic diseases lie in non‑coding regions of the genome — regulatory sequences that affect when, where and how genes are expressed rather than altering the protein structure directly. For example, loci involved in epithelial‑barrier integrity (such as FLG and SERPINB7) and immune‑system orchestration (such as the HLA region and IL4) repeatedly emerge in genome‑wide association studies of allergy, asthma, atopic dermatitis and food‑sensitisation.

At the same time, epigenetic mechanisms (including DNA methylation, histone marks and microRNAs) modulate gene expression in response to environmental exposures (diet, pollutants, stress) and are increasingly recognised as key mediators of allergy risk. The integration of genomic and epigenomic data is advancing our understanding of how inherited susceptibility and environment collaborate to shape allergic disease onset, severity and phenotype.

Clinical Implications and Future Directions

Recognizing the hereditary aspect of allergies has important clinical implications. Genetic screening and polygenic risk scoring may enable identification of individuals at elevated risk, allowing for earlier interventions and preventive strategies. Moreover, improved comprehension of genetic mechanisms fosters the development of targeted treatments, including immunotherapies that modulate immune responses more precisely.

Klaus Bønnelykke from Clinical Research Associate Professor of Clinical Medicine, University of Copenhagen believes that large‑scale genetic studies have identified dozens of new gene regions linked to hay fever and other allergic diseases, and while genes contribute significantly to susceptibility, the rapid rise in allergy rates – particularly in westernised populations – points to major environmental and lifestyle changes interacting with genetic risk.

Allergies arise from a multifaceted interaction between inherited genetic susceptibility and environmental exposures. Heredity primarily influences the predisposition to produce allergic responses, as demonstrated by family and twin studies, and through identification of numerous gene variants involved in immune regulation and epithelial barrier integrity.

Epigenetic modifications further shape allergy risk by mediating the impact of environmental factors on gene expression. Continued research, emphasizing diverse populations and integrated genomic data, promises to deepen understanding, improve diagnostics, and transform care for individuals affected by allergic diseases.