FOOD ALLERGY (FA) risk was further clarified at the genetic level after a large genome-wide association meta-analysis identified 37 suggestive risk variants across children and adults.
FA is an immune-mediated condition, often driven by immunoglobulin E (IgE), in which specific foods trigger reproducible adverse reactions. Prevalence has increased steadily over recent decades, yet the genetic architecture of food allergy remains incompletely understood. Previous genome-wide association studies (GWAS) have been limited by modest sample sizes and inconsistent definitions of FA.
To address this, researchers conducted a genome-wide association meta-analysis across up to 16 cohorts of European ancestry, including 229,426 adults and 14,234 children. A multi-phenotype approach was used, incorporating self-reported FA, doctor-diagnosed FA, food-specific IgE sensitisation, and combined definitions. Analyses were adjusted for sex, age, principal components, and study-specific confounders, with additional sensitivity models adjusting for hay fever.
Food Allergy Genetic Associations Identified
The study identified 37 single nucleotide polymorphisms (SNPs) reaching suggestive significance (p<1×10⁻⁶). Two variants achieved genome-wide significance in adults. The first, rs116936231 in FGL1, was associated with doctor-diagnosed FA plus food-specific IgE sensitisation and remained significant after additional adjustment for hay fever. The second, rs8022829 in the AKAP6–NPAS3 region, reached genome-wide significance only in the hay fever-adjusted model.
However, neither variant was validated in external replication cohorts nor in cases defined by oral food challenge, considered the gold standard for food allergy diagnosis. The researchers also identified three previously reported SNPs associated with food allergy and broader atopic disease, reinforcing shared genetic pathways between FA and other allergic conditions.
Definitions Shape Food Allergy Genetic Signals
Importantly, the study demonstrated genetic differences across food allergy phenotypes, indicating that the choice of definition influenced the observed associations. This finding underscored the need for harmonised diagnostic criteria in genetic research on food allergy.
While the large sample size strengthened statistical power, limitations included restriction to individuals of European ancestry and the lack of replication for newly identified genome-wide significant loci.
Overall, the findings expanded understanding of food allergy genetics and underscored the need for unified diagnostic criteria. Larger, multi-ethnic studies using consistent, gold-standard phenotyping will be essential to translate these discoveries into risk prediction tools and targeted prevention strategies for patients with food allergy.
Reference
Maier L et al. Meta-analysis of genome-wide association studies of food allergy and IgE-sensitization. J Allergy Clin Immunol. 2026; DOI:10.1016/j.jaci.2026.02.012.
