Meta-analysis of genome-wide association studies of food allergy and IgE-sensitization.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Authors
Maier Maier, Sun Sun, Kronberg Kronberg, Abner Abner, , Coley Coley, Marenholz Marenholz, Weiss Weiss, Foraita Foraita, Karramass Karramass, Mykkänen Mykkänen, Hernandez-Pacheco Hernandez-Pacheco, Wang Wang, Kitaba Kitaba, Pechlivanis Pechlivanis, Bouzigon Bouzigon, Tingskov Pedersen Tingskov Pedersen, Schoos Schoos, Curtin Curtin, Kress Kress, Hernangomez-Laderas Hernangomez-Laderas, Foppiano Foppiano, Ashley Ashley, Batini Batini, Bryant Bryant, Homuth Homuth, Gieger Gieger, Gilles Gilles, Lyytikäinen Lyytikäinen, Rovio Rovio, Pahkala Pahkala, Vernet Vernet, Valenta Valenta, Llop Llop, Torrent Torrent, Böck Böck, Tang Tang, Schmidt-Weber Schmidt-Weber, Metspalu Metspalu, Esko Esko, Sprikkelman Sprikkelman, John John, Lee Lee, Beyer Beyer, Völzke Völzke, Pigeot Pigeot, Traidl-Hoffmann Traidl-Hoffmann, Duijts Duijts, Lu Lu, Raitakari Raitakari, Lehtimäki Lehtimäki, Kähönen Kähönen, Tio Tio, Melén Melén, Pennell Pennell, Holloway Holloway, von Mutius von Mutius, Siroux Siroux, Bønnelykke Bønnelykke, Custovic Custovic, Simpson Simpson, Schikowski Schikowski, Bilbao Bilbao, Schaub Schaub, Peters Peters, Kersten Kersten, Vonk Vonk, Thiering Thiering, Peters Peters, Koppelman Koppelman, Standl Standl
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