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

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

doi:10.1016/j.jaci.2026.02.012

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

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

^*Corresponding author af dette arbejde

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.

Originalsprog	Engelsk
Tidsskrift	The Journal of allergy and clinical immunology
ISSN	0091-6749
DOI	https://doi.org/10.1016/j.jaci.2026.02.012
Status	E-pub ahead of print - 20 feb. 2026

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10.1016/j.jaci.2026.02.012Licens: CC BY-NC

Citationsformater

Maier, L., Sun, Y., Kronberg, J., Abner, E., Coley, K., Marenholz, I., Weiss, S., Foraita, R., Karramass, T., Mykkänen, J., Hernandez-Pacheco, N., Wang, C. A., Kitaba, N. T., Pechlivanis, S., Bouzigon, E., Tingskov Pedersen, C. E., Schoos, A.-M. M., Curtin, J., Kress, S., ... Estonian Biobank Research Team (2026). Meta-analysis of genome-wide association studies of food allergy and IgE-sensitization. The Journal of allergy and clinical immunology. Advance online publication. https://doi.org/10.1016/j.jaci.2026.02.012

Maier, L, Sun, Y, Kronberg, J, Abner, E, Coley, K, Marenholz, I, Weiss, S, Foraita, R, Karramass, T, Mykkänen, J, Hernandez-Pacheco, N, Wang, CA, Kitaba, NT, Pechlivanis, S, Bouzigon, E, Tingskov Pedersen, CE , Schoos, A-MM, Curtin, J, Kress, S, Hernangomez-Laderas, A, Foppiano, F, Ashley, S, Batini, C, Bryant, L, Homuth, G, Gieger, C, Gilles, S, Lyytikäinen, L-P, Rovio, S, Pahkala, K, Vernet, R, Valenta, R, Llop, S, Torrent, M, Böck, A, Tang, MLK, Schmidt-Weber, CB, Metspalu, A, Esko, T, Sprikkelman, AB, John, C, Lee, Y-A, Beyer, K, Völzke, H, Pigeot, I, Traidl-Hoffmann, C, Duijts, L, Lu, H, Raitakari, OT, Lehtimäki, T, Kähönen, M, Tio, CHL, Melén, E, Pennell, CE, Holloway, JW, von Mutius, E, Siroux, V, Bønnelykke, K, Custovic, A, Simpson, A, Schikowski, T, Bilbao, JR, Schaub, B, Peters, R, Kersten, ETG, Vonk, JM, Thiering, E, Peters, A, Koppelman, GH, Standl, M & Estonian Biobank Research Team 2026, 'Meta-analysis of genome-wide association studies of food allergy and IgE-sensitization', The Journal of allergy and clinical immunology. https://doi.org/10.1016/j.jaci.2026.02.012

@article{8f6ad613ff2b49509cb1ccac8fbb9bb4,

title = "Meta-analysis of genome-wide association studies of food allergy and IgE-sensitization",

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.",

author = "Lisa Maier and Yidan Sun and Jaanika Kronberg and Erik Abner and Kayesha Coley and Ingo Marenholz and Stefan Weiss and Ronja Foraita and Tarik Karramass and Juha Mykk{\"a}nen and Natalia Hernandez-Pacheco and Wang, \{Carol A\} and Kitaba, \{Negusse T\} and Sonali Pechlivanis and Emmanuelle Bouzigon and \{Tingskov Pedersen\}, \{Casper E\} and Schoos, \{Ann-Marie M\} and John Curtin and Sara Kress and Alba Hernangomez-Laderas and Francesco Foppiano and Sarah Ashley and Chiara Batini and Luke Bryant and Georg Homuth and Christian Gieger and Stefanie Gilles and Leo-Pekka Lyytik{\"a}inen and Suvi Rovio and Katja Pahkala and Rapha{\"e}l Vernet and Rudolph Valenta and Sabrina Llop and Maties Torrent and Andreas B{\"o}ck and Tang, \{Mimi L K\} and Schmidt-Weber, \{Carsten B\} and Andres Metspalu and T{\~o}nu Esko and Sprikkelman, \{Aline B\} and Catherine John and Young-Ae Lee and Kirsten Beyer and Henry V{\"o}lzke and Iris Pigeot and Claudia Traidl-Hoffmann and Liesbeth Duijts and Haojie Lu and Raitakari, \{Olli T\} and Terho Lehtim{\"a}ki and Mika K{\"a}h{\"o}nen and Tio, \{Chris H L\} and Erik Mel{\'e}n and Pennell, \{Craig E\} and Holloway, \{John W\} and \{von Mutius\}, Erika and Val{\'e}rie Siroux and Klaus B{\o}nnelykke and Adnan Custovic and Angela Simpson and Tamara Schikowski and Bilbao, \{Jose Ramon\} and Bianca Schaub and Rachel Peters and Kersten, \{Elin T G\} and Vonk, \{Judith M\} and Elisabeth Thiering and Annette Peters and Koppelman, \{Gerard H\} and Marie Standl and \{Estonian Biobank Research Team\}",

note = "Copyright {\textcopyright} 2026. Published by Elsevier Inc.",

year = "2026",

month = feb,

day = "20",

doi = "10.1016/j.jaci.2026.02.012",

language = "English",

journal = "The Journal of allergy and clinical immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Meta-analysis of genome-wide association studies of food allergy and IgE-sensitization

AU - Maier, Lisa

AU - Sun, Yidan

AU - Kronberg, Jaanika

AU - Abner, Erik

AU - Coley, Kayesha

AU - Marenholz, Ingo

AU - Weiss, Stefan

AU - Foraita, Ronja

AU - Karramass, Tarik

AU - Mykkänen, Juha

AU - Hernandez-Pacheco, Natalia

AU - Wang, Carol A

AU - Kitaba, Negusse T

AU - Pechlivanis, Sonali

AU - Bouzigon, Emmanuelle

AU - Tingskov Pedersen, Casper E

AU - Schoos, Ann-Marie M

AU - Curtin, John

AU - Kress, Sara

AU - Hernangomez-Laderas, Alba

AU - Foppiano, Francesco

AU - Ashley, Sarah

AU - Batini, Chiara

AU - Bryant, Luke

AU - Homuth, Georg

AU - Gieger, Christian

AU - Gilles, Stefanie

AU - Lyytikäinen, Leo-Pekka

AU - Rovio, Suvi

AU - Pahkala, Katja

AU - Vernet, Raphaël

AU - Valenta, Rudolph

AU - Llop, Sabrina

AU - Torrent, Maties

AU - Böck, Andreas

AU - Tang, Mimi L K

AU - Schmidt-Weber, Carsten B

AU - Metspalu, Andres

AU - Esko, Tõnu

AU - Sprikkelman, Aline B

AU - John, Catherine

AU - Lee, Young-Ae

AU - Beyer, Kirsten

AU - Völzke, Henry

AU - Pigeot, Iris

AU - Traidl-Hoffmann, Claudia

AU - Duijts, Liesbeth

AU - Lu, Haojie

AU - Raitakari, Olli T

AU - Lehtimäki, Terho

AU - Kähönen, Mika

AU - Tio, Chris H L

AU - Melén, Erik

AU - Pennell, Craig E

AU - Holloway, John W

AU - von Mutius, Erika

AU - Siroux, Valérie

AU - Bønnelykke, Klaus

AU - Custovic, Adnan

AU - Simpson, Angela

AU - Schikowski, Tamara

AU - Bilbao, Jose Ramon

AU - Schaub, Bianca

AU - Peters, Rachel

AU - Kersten, Elin T G

AU - Vonk, Judith M

AU - Thiering, Elisabeth

AU - Peters, Annette

AU - Koppelman, Gerard H

AU - Standl, Marie

AU - Estonian Biobank Research Team

PY - 2026/2/20

Y1 - 2026/2/20

N2 - 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.

AB - 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.

U2 - 10.1016/j.jaci.2026.02.012

DO - 10.1016/j.jaci.2026.02.012

M3 - Review

C2 - 41724405

SN - 0091-6749

JO - The Journal of allergy and clinical immunology

JF - The Journal of allergy and clinical immunology

ER -

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

Abstract

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