Food Allergy Genetics and Epigenetics: A Review of Genome-Wide Association Studies

doi:10.1111/all.16429

Review

. 2025 Jan;80(1):106-131.

doi: 10.1111/all.16429. Epub 2024 Dec 19.

Food Allergy Genetics and Epigenetics: A Review of Genome-Wide Association Studies

Aleix Arnau-Soler^{1

2

3

4}, Bénédicte L Tremblay⁵, Yidan Sun^{6

7}, Anne-Marie Madore⁵, Mathieu Simard⁵, Elin T G Kersten^{6

7}, Ahla Ghauri^{1

2

3

4}, Ingo Marenholz^{1

2

3}, Thomas Eiwegger^{8

9

10

11

12}, Elinor Simons¹³, Edmond S Chan¹⁴, Kari Nadeau¹⁵, Vanitha Sampath¹⁵, Bruce D Mazer¹⁶, Susan Elliott¹⁷, Christine Hampson¹⁸, Lianne Soller¹⁴, Andrew Sandford^{19

20}, Philippe Begin^{21

22}, Jennie Hui²³, Bethany F Wilken²⁴, Jennifer Gerdts²⁵, Adrienn Bourkas²⁴, Anne K Ellis²⁶, Denitsa Vasileva^{19

20}, Ann Clarke²⁷, Aida Eslami²⁸, Moshe Ben-Shoshan²⁹, David Martino³⁰, Denise Daley^{19

20}, Gerard H Koppelman^{6

7}, Catherine Laprise⁵, Young-Ae Lee^{1

2

3

4}, Yuka Asai³¹

Affiliations

¹ Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
² Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
³ Experimental and Clinical Research Center, a Joint Cooperation of Max Delbruck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁴ German Center for Child and Adolescent Health (DZKJ), Berlin, Germany.
⁵ Département Des Sciences Fondamentales, Université du Québec à Chicoutimi, Saguenay, Quebec, Canada.
⁶ Department of Pediatric Pulmonology and Pediatric Allergology, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, the Netherlands.
⁷ University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
⁸ Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
⁹ Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria.
¹¹ Department of Pediatric and Adolescent Medicine, University Hospital St. Pölten, St. Pölten, Austria.
¹² Department of Paediatrics, Division of Clinical Immunology and Allergy, Food Allergy and Anaphylaxis Program, the Hospital for Sick Children, The University of Toronto, Toronto, Ontario, Canada.
¹³ Section of Allergy & Clinical Immunology, Department of Pediatrics & Child Health, University of Manitoba, Children's Hospital Research Institute, Winnipeg, Manitoba, Canada.
¹⁴ Division of Allergy, Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada.
¹⁵ Department of Environmental Studies, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
¹⁶ Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
¹⁷ Department of Geography and Environmental Management, University of Waterloo, Waterloo, Ontario, Canada.
¹⁸ The Sandbox Project, Toronto, Ontario, Canada.
¹⁹ Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
²⁰ Centre for Heart Lung Innovation, Vancouver, British Columbia, Canada.
²¹ Department of Pediatrics, Service of Allergy and Clinical Immunology, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada.
²² Department of Medicine, Service of Allergy and Clinical Immunology, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
²³ School of Population Health, University of Western Australia, Perth, Western Australia, Australia.
²⁴ School of Medicine, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
²⁵ Food Allergy Canada, Toronto, Ontario, Canada.
²⁶ Division of Allergy & Immunology, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
²⁷ Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
²⁸ Département de médecine Sociale et préventive, Faculté de médecine, Université Laval, Quebec, Canada.
²⁹ Division of Allergy and Clinical Immunology, Department of Pediatrics, Montréal Children's Hospital, McGill University Health Centre, Montréal, Quebec, Canada.
³⁰ Wal-Yan Respiratory Research Centre, Telethon Kids Institute, Perth, Australia.
³¹ Division of Dermatology, Department of Medicine, Queen's University, Kingston, Ontario, Canada.

PMID: 39698764
PMCID: PMC11724255
DOI: 10.1111/all.16429

Review

Food Allergy Genetics and Epigenetics: A Review of Genome-Wide Association Studies

Aleix Arnau-Soler et al. Allergy. 2025 Jan.

. 2025 Jan;80(1):106-131.

doi: 10.1111/all.16429. Epub 2024 Dec 19.

Authors

Affiliations

¹ Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
² Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
³ Experimental and Clinical Research Center, a Joint Cooperation of Max Delbruck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁴ German Center for Child and Adolescent Health (DZKJ), Berlin, Germany.
⁵ Département Des Sciences Fondamentales, Université du Québec à Chicoutimi, Saguenay, Quebec, Canada.
⁶ Department of Pediatric Pulmonology and Pediatric Allergology, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, the Netherlands.
⁷ University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
⁸ Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
⁹ Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria.
¹¹ Department of Pediatric and Adolescent Medicine, University Hospital St. Pölten, St. Pölten, Austria.
¹² Department of Paediatrics, Division of Clinical Immunology and Allergy, Food Allergy and Anaphylaxis Program, the Hospital for Sick Children, The University of Toronto, Toronto, Ontario, Canada.
¹³ Section of Allergy & Clinical Immunology, Department of Pediatrics & Child Health, University of Manitoba, Children's Hospital Research Institute, Winnipeg, Manitoba, Canada.
¹⁴ Division of Allergy, Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada.
¹⁵ Department of Environmental Studies, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
¹⁶ Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
¹⁷ Department of Geography and Environmental Management, University of Waterloo, Waterloo, Ontario, Canada.
¹⁸ The Sandbox Project, Toronto, Ontario, Canada.
¹⁹ Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
²⁰ Centre for Heart Lung Innovation, Vancouver, British Columbia, Canada.
²¹ Department of Pediatrics, Service of Allergy and Clinical Immunology, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada.
²² Department of Medicine, Service of Allergy and Clinical Immunology, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
²³ School of Population Health, University of Western Australia, Perth, Western Australia, Australia.
²⁴ School of Medicine, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
²⁵ Food Allergy Canada, Toronto, Ontario, Canada.
²⁶ Division of Allergy & Immunology, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
²⁷ Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
²⁸ Département de médecine Sociale et préventive, Faculté de médecine, Université Laval, Quebec, Canada.
²⁹ Division of Allergy and Clinical Immunology, Department of Pediatrics, Montréal Children's Hospital, McGill University Health Centre, Montréal, Quebec, Canada.
³⁰ Wal-Yan Respiratory Research Centre, Telethon Kids Institute, Perth, Australia.
³¹ Division of Dermatology, Department of Medicine, Queen's University, Kingston, Ontario, Canada.

PMID: 39698764
PMCID: PMC11724255
DOI: 10.1111/all.16429

Abstract

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.

Keywords: allergy; epigenetics; food allergy; genetics; inheritance.

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Conflict of interest statement

KN currently reports grants from National Institute of Allergy and Infectious Diseases (NIAID), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Environmental Health Sciences (NIEHS); Stock options from Phylaxis, IgGenix, Seed Health, ClostraBio, Cour; Advisory board for Aravax, Consultant for Excellergy, and Regeneron; Co‐founder of IgGenix; National Scientific Committee member at Immune Tolerance Network (ITN), and National Institutes of Health (NIH) clinical research centers; Scientific advisor for World Health Organization; Patents include, “Mixed allergen com‐position and methods for using the same,” “Granulocyte‐based methods for detecting and monitoring immune system disorders,” and “Methods and Assays for Detecting and Quantifying Pure Subpopulations of White Blood Cells in Immune System Disorders.” PB reports grants from Sanofi, Novartis, and DBV technologies and honoraria from Prizer, Sanofi, Novartis, ALK, DBV technologies, and Astra‐Zeneca. JH has no conflicts of interest to declare. ESC has received research support from DBV Technologies; and has been a member of advisory boards for Pfizer, Miravo, Medexus, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi, Bausch Health, Avir Pharma, AstraZeneca, ALK, Alladapt. In the past, Dr. Anne K. Ellis has participated in advisory boards for ALK Abello, AstraZeneca, Bausch Health, LEO Pharma, Miravo, Merck, Novartis, has been a speaker for ALK Abello, AstraZeneca, Bausch, Miravo, Medexus, Mylan, Novartis, Pfizer, Sanofi, StallergenesGreer and Regeneron. Her institution has received research grants from ALK Abello, Aralez, AstraZeneca, Bayer LLC, Medexus, Novartis, Sanofi, and Regeneron. She has also served as an independent consultant to Bayer LLC, Pharming, and Regeneron. YA reports grants from the Canadian Dermatology Foundation, the Eczema Society of Canada and unrestricted institutional research support from Sanofi, AbbVie, Pfizer, Novartis, Leo Pharma, performs clinical trials for Leo Pharma and Novartis, and has received speakers' or advisory board honoraria from Pfizer, Sun Pharma, Taro, Sanofi, Eli Lilly, Abbvie, Novartis, Searchlight Pharma, Leo Pharma, UCB, L'Oreal, Boehringer Ingelheim, Kyowa Kirin, Arcutis, Bristol Myers Squibb, Incyte, and Recordati. GHK reports grants from the Netherlands Lung Foundation, ZON‐MW, Ubbo Emmius Foundation, GSK, Vertex, TEVA the Netherlands; all outside the submitted work. His institution has received speakers' honoraria from the exquAIro foundation, Sanofi, Astra‐Zeneca, and Boehringer Ingelheim. MBS is a member of advisory boards for Pfizer, Miravo, Medexus, Sanofi, Novartis, and reports speakers honoraria from Novartis, Sanofi, Medexus, and StallergenesGreer. His institution has received research support from Novartis, Sanofi, and DBV Technologies. TE reports personal fees from Danone/Nutricia/Milupa, grants from DBV, non‐financial support from Novartis, personal fees from ThermoFisher, personal fees from Aimmune, grants and personal fees from ALK, non‐financial support from MADX, personal fees from EFSA, outside the submitted work; he is Co‐I or scientific lead in three investigator initiated oral immunotherapy trials supported by the Food Allergy and Anaphylaxis Program Sickkids and serve as associate editor for Allergy. he recently was and is acting site PI of company sponsored trials by DBV, Novartis and Stallergen. LS, CL, MS, BLT, AMM, MBS, AEC, DV, CH, AJS, BFW, AB, AE, AAS, YS, ET, GK, DD, DM, SE, JG, VS, BDM, and YL report no conflicts of interest.

Figures

**FIGURE 1**
Review of genetic and epigenetic mechanisms. Double‐stranded DNA makes up the genome and is coiled to make chromatin fibers and then wrapped around histones to make chromosomes. Genomic changes called single nucleotide polymorphisms (SNP) are a one base‐pair change in germline DNA. These can occur both in exons (protein coding) and introns (non‐coding regions, which often have regulatory function). Changes in DNA that involve a change in repetition of sections of the genome are known as copy number variants (CNV). DNA must be accessible in order to be transcribed into messenger RNAs (mRNA), which constitute the transcriptome. mRNA are then translated into proteins which collectively make up the proteome. Epigenetic mechanisms—shaped by external factors—include DNA methylation, histone modification and non‐coding RNA. Long non‐coding and micro RNAs (miRNA; short single strands of RNA) can bind to transcribed mRNA affecting translation. Genetic and epigenetic modifications can impact protein expression, including a complete lack of protein production, a change in protein levels, or a change in protein sequence that leads to a truncated protein or a protein with impaired function. This figure has been created with BioRender.com.

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References

1. Warren C. M., Jiang J., and Gupta R. S., “Epidemiology and Burden of Food Allergy,” Current Allergy and Asthma Reports 20, no. 2 (2020): 6. - PMC - PubMed
1. Koplin J. J., Allen K. J., Gurrin L. C., et al., “The Impact of Family History of Allergy on Risk of Food Allergy: A Population‐Based Study of Infants,” International Journal of Environmental Research and Public Health 10, no. 11 (2013): 5364–5377. - PMC - PubMed
1. Guarnieri K. M., Saba N. K., Schwartz J. T., et al., “Food Allergy Characteristics Associated With Coexisting Eosinophilic Esophagitis in FARE Registry Participants,” Journal of Allergy and Clinical Immunology in Practice 11, no. 5 (2023): 1509–1521.e1506. - PMC - PubMed
1. Ullemar V., Magnusson P. K., Lundholm C., et al., “Heritability and Confirmation of Genetic Association Studies for Childhood Asthma in Twins,” Allergy 71, no. 2 (2016): 230–238. - PubMed
1. Sicherer S. H., Furlong T. J., Maes H. H., Desnick R. J., Sampson H. A., and Gelb B. D., “Genetics of Peanut Allergy: A Twin Study,” Journal of Allergy and Clinical Immunology 106, no. 1 Pt 1 (2000): 53–56. - PubMed

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[1] Warren C. M., Jiang J., and Gupta R. S., “Epidemiology and Burden of Food Allergy,” Current Allergy and Asthma Reports 20, no. 2 (2020): 6. - PMC - PubMed

[2] Warren C. M., Jiang J., and Gupta R. S., “Epidemiology and Burden of Food Allergy,” Current Allergy and Asthma Reports 20, no. 2 (2020): 6. - PMC - PubMed

[3] Koplin J. J., Allen K. J., Gurrin L. C., et al., “The Impact of Family History of Allergy on Risk of Food Allergy: A Population‐Based Study of Infants,” International Journal of Environmental Research and Public Health 10, no. 11 (2013): 5364–5377. - PMC - PubMed

[4] Koplin J. J., Allen K. J., Gurrin L. C., et al., “The Impact of Family History of Allergy on Risk of Food Allergy: A Population‐Based Study of Infants,” International Journal of Environmental Research and Public Health 10, no. 11 (2013): 5364–5377. - PMC - PubMed

[5] Guarnieri K. M., Saba N. K., Schwartz J. T., et al., “Food Allergy Characteristics Associated With Coexisting Eosinophilic Esophagitis in FARE Registry Participants,” Journal of Allergy and Clinical Immunology in Practice 11, no. 5 (2023): 1509–1521.e1506. - PMC - PubMed

[6] Guarnieri K. M., Saba N. K., Schwartz J. T., et al., “Food Allergy Characteristics Associated With Coexisting Eosinophilic Esophagitis in FARE Registry Participants,” Journal of Allergy and Clinical Immunology in Practice 11, no. 5 (2023): 1509–1521.e1506. - PMC - PubMed

[7] Ullemar V., Magnusson P. K., Lundholm C., et al., “Heritability and Confirmation of Genetic Association Studies for Childhood Asthma in Twins,” Allergy 71, no. 2 (2016): 230–238. - PubMed

[8] Ullemar V., Magnusson P. K., Lundholm C., et al., “Heritability and Confirmation of Genetic Association Studies for Childhood Asthma in Twins,” Allergy 71, no. 2 (2016): 230–238. - PubMed

[9] Sicherer S. H., Furlong T. J., Maes H. H., Desnick R. J., Sampson H. A., and Gelb B. D., “Genetics of Peanut Allergy: A Twin Study,” Journal of Allergy and Clinical Immunology 106, no. 1 Pt 1 (2000): 53–56. - PubMed

[10] Sicherer S. H., Furlong T. J., Maes H. H., Desnick R. J., Sampson H. A., and Gelb B. D., “Genetics of Peanut Allergy: A Twin Study,” Journal of Allergy and Clinical Immunology 106, no. 1 Pt 1 (2000): 53–56. - PubMed

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Food Allergy Genetics and Epigenetics: A Review of Genome-Wide Association Studies

Affiliations

Food Allergy Genetics and Epigenetics: A Review of Genome-Wide Association Studies

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Conflict of interest statement

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