Genome‐Wide Association Study Reveals a Causal Relationship Between Allergic Rhinitis and Hazelnut Allergy

ABSTRACT Background Little is known about the genetics of food allergy (FA) to various allergens and the heterogeneity of FA in adults. Objective We aimed to investigate genetic susceptibility to FA in an adult population and to assess the association between secondary FA and allergic rhinitis (AR). Methods FA and allergen‐specific FA were defined based on in‐depth questionnaires and a previously published FA algorithm in the Lifelines. We performed a series of genome‐wide association studies (GWAS) on FA and nine allergen‐specific (e.g., hazelnut) FA in 21,353 adults in Lifelines. Single nucleotide polymorphisms (SNPs) ( p < 1E‐5) were replicated in a second independent set of 15,518 adults participating in the Lifelines followed by meta‐analysis of the results of the two datasets. We subsequently investigated the causal relationship of AR to FA using Mendelian randomization (MR) analysis. Results We observed co‐occurrence of tree nuts and apple FA, with over 80% of this group also reporting AR. After meta‐analysis, we identified one genome‐wide significant locus near HLA‐DPA1 associated with self‐reported hazelnut allergy (hazelnutFA), of which the top SNP is rs5025825 ( p = 2.51E‐9, OR = 1.43). Two‐sample MR indicated that AR is a significant causal risk factor for hazelnutFA ( p ‐IVW = 5.27E‐10, β = 5.90, p ‐pleiotropy = 0.46). Conclusion Our questionnaire enabled a large GWAS on self‐reported FA in Dutch adults. We report one novel locus in the human leukocyte antigens (HLA) region associated with hazelnutFA, implying an association with antigen recognition. Our findings genetically link secondary FA to AR in adults.