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In this review, we provide an overview of food allergy genetics and epigenetics aimed at clinicians and researchers. This includes a brief review of the current understanding of genetic and epigenetic mechanisms, inheritance of food allergy, as well as a discussion of advantages and limitations of the different types of studies in genetic research. We specifically focus on the results of genome-wide association studies in food allergy, which have identified 16 genetic variants that reach genome-wide significance, many of which overlap with other allergic diseases, including asthma, atopic dermatitis, and allergic rhinitis. Identified genes for food allergy are mainly involved in epithelial barrier function (e.g., FLG, SERPINB7) and immune function (e.g., HLA, IL4). Epigenome-wide significant findings at 32 loci are also summarized as well as 14 additional loci with significance at a false discovery of < 1 × 10 -4 . Integration of epigenetic and genetic data is discussed in the context of disease mechanisms, many of which are shared with other allergic diseases. The potential utility of genetic and epigenetic discoveries is deliberated. In the future, genetic and epigenetic markers may offer ways to predict the presence or absence of clinical IgE-mediated food allergy among sensitized individuals, likelihood of development of natural tolerance, and response to immunotherapy., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: A genetic defect in the epidermal barrier protein filaggrin (FLG) plays a major role in the etiology of eczema and associated allergic airways diseases. However, it is still controversial to what extend loss-of-function (LOF) mutations in FLG contribute to the development and persistence of food allergies., Objectives: This study tested association of FLG LOF mutations with allergic reactions to diverse foods and investigated their potential effect on the persistence of early food allergies., Methods: This study recruited 890 children with challenge-proven food allergy for the German Genetics of Food Allergy Study (GOFA). Longitudinal data were available for 684 children. All children were clinically characterized, including their allergic responses to specific foods, and genotyped for the 4 most common LOF mutations in FLG; R501X, 2282del4, R2447X, and S3247X. Associations between FLG mutations and food allergies were analyzed by logistic regression using the German Multicenter Allergy Study cohort as the control population., Results: FLG mutations were associated with allergies to diverse foods including hen's egg (HE), cow's milk (CM), peanut, hazelnut, fish, soy, cashew, walnut, and sesame with similar risk estimates. Effects remained significant after adjusting for the eczema status. Interestingly, FLG mutations increased the risk of a persistent course of HE and CM allergy., Conclusions: Using the gold standard for food allergy diagnosis, this study demonstrates that FLG LOF mutations confer a risk of any food allergy independent of eczema. These mutations predispose to the persistence of HE and CM allergy and should be considered in the assessment of tolerance development., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)