Meta-analysis of genome-wide association studies of food allergy and IgE-sensitization - UTU Research Portal

A1 Refereed original research article in a scientific journal

Meta-analysis of genome-wide association studies of food allergy and IgE-sensitization

Authors: Maier, Lisa; Sun, Yidan; Kronberg, Jaanika; Abner, Erik; Coley, Kayesha; Marenholz, Ingo; Weiss, Stefan; Foraita, Ronja; Karramass, Tarik; Mykkänen, Juha; Hernandez-Pacheco, Natalia; Wang, Carol A.; Kitaba, Negusse T.; Pechlivanis, Sonali; Bouzigon, Emmanuelle; Tingskov Pedersen, Casper E.; Schoos, Ann-Marie M.; Curtin, John; Kress, Sara; Hernangomez-Laderas, Alba; Foppiano, Francesco; Ashley, Sarah; Batini, Chiara; Bryant, Luke; Homuth, Georg; Gieger, Christian; Gilles, Stefanie; Lyytikäinen, Leo-Pekka; Rovio, Suvi; Pahkala, Katja; Vernet, Raphaël; Valenta, Rudolph; Llop, Sabrina; Torrent, Maties; Böck, Andreas; Tang, Mimi L. K.; Schmidt-Weber, Carsten B.; Metspalu, Andres; Esko, Tõnu; Sprikkelman, Aline B.; John, Catherine; Lee, Young-Ae; Beyer, Kirsten; Völzke, Henry; Pigeot, Iris; Traidl-Hoffmann, Claudia; Duijts, Liesbeth; Lu, Haojie; Raitakari, Olli T.; Lehtimäki, Terho; Kähönen, Mika; Tio, Chris H. L.; Melén, Erik; Pennell, Craig E.; Holloway, John W.; von Mutius, Erika; Siroux, Valérie; Bønnelykke, Klaus; Custovic, Adnan; Simpson, Angela; Schikowski, Tamara; Bilbao, Jose Ramon; Schaub, Bianca; Peters, Rachel; Kersten, Elin T. G.; Vonk, Judith M.; Thiering, Elisabeth; Peters, Annette; Koppelman, Gerard H.; Standl, Marie

Publisher: Elsevier

Publication year: 2026

Journal: Journal of Allergy and Clinical Immunology

ISSN: 0091-6749

eISSN: 1097-6825

DOI: https://doi.org/10.1016/j.jaci.2026.02.012

Publication's open availability at the time of reporting: Open Access

Publication channel's open availability : Partially Open Access publication channel

Web address : https://doi.org/10.1016/j.jaci.2026.02.012

Abstract

Background

Food allergies (FA) arise from a complex interplay between an individual’s genetic predisposition and environmental factors and their prevalence is increasing. Genome-wide association studies (GWAS) to date have been hindered by small sample sizes and varying FA definitions.

Objective

Identify novel food allergy risk loci by conducting a GWAS meta-analysis in children and adults using a multi-phenotype approach to ensure the trade-off between sufficient sample size and valid FA definitions.

Methods

Analyses were conducted separately in children and adults based on the following FA phenotypes: self-report, doctors-diagnosis, food-specific sensitization, and doctors-diagnosis plus food-specific sensitization. GWAS from up to 16 cohorts of European ancestry including 229,426 adults and 14,234 children were meta-analyzed. Models were adjusted for sex, age, principal components, and if applicable, further study-specific confounders. Sensitivity models were additionally adjusted for hay fever. Replication was conducted in additional external cohorts and a validation in oral food challenge-defined FA cases.

Results

37 SNPs met suggestive significance (p-value < 1x10^-6), with two reaching genome-wide significance: rs116936231 (FGL1) in adult doctors-diagnosed FA plus food-specific sensitization phenotype (stable after additional hay fever adjustment) and rs8022829 (AKAP6-NPAS3) which was significant only in the hay fever-adjusted model in adults. However, neither variant was validated. Further, we identified three SNPs previously reported for FA and atopic diseases.

Conclusion

This study identified 37 SNPs suggestively associated with FA and demonstrated genetic differences across phenotypes. It highlights the need for a unified FA definition and sheds light on its shared genetic architecture with allergies.

Funding information in the publication:
LM and MS have received funding from the Federal Ministry of Education and Research (BMBF) under the ABROGATE project (grant agreement No. 01EA2106B), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 949906) and the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) as part of the German Center for Child and Adolescent Health (DZKJ) under the funding code 01GL2406C. YS was supported by the Chinese Scholarship Council. NH-P was supported with a Medium-Term Research Fellowship by the European Academy of Allergy and Clinical Immunology (EAACI) and a Long-Term Research Fellowship by the European Respiratory Society (ERS) (LTRF202101-00861). The IUF is funded by the federal and state governments - the Ministry of Culture and Science of North Rhine-Westphalia (MKW) and the Federal Ministry of Research, Technology and Space (BMFTR). RV is funded by the Danube Allergy Research Cluster of the Country of Lower Austria. Further details of the many funding organizations that supported this study and the participating cohorts can be found in this articles Supplementary Information. Cohort-specific funding can be found in Supplementary Note.