Meta-analysis of genome-wide association studies of food allergy and IgE sensitization.
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Maier Lisa, Sun Yidan, Kronberg Jaanika, Abner Erik, Estonian Biobank Research Team, 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-Emil, Schoos Ann-Marie M, Curtin John A, 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 Rudolf, 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, Thio 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
Аннотация
OBJECTIVE: We sought to identify novel FA risk loci by conducting a genome-wide association study meta-analysis in children and adults by using a multiphenotype approach to ensure a good trade-off between sufficient sample size and valid FA definitions.
METHODS: Analyses were conducted separately in children and adults on the basis of the following FA phenotypes: self-report, doctor diagnosis, food-specific sensitization, and doctor diagnosis plus food-specific sensitization. A meta-analysis was performed of genome-wide association studies from up to 16 cohorts of people of European ancestry including 229,426 adults and 14,234 children. 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: Thirty-seven single nucleotide polymorphisms met suggestive significance (P < 1 × 10-6), with two reaching genome-wide significance: rs116936231 (FGL1) in adult doctor-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 3 single nucleotide polymorphisms previously reported for FA and atopic disease.
CONCLUSION: This study identified 37 single nucleotide polymorphisms suggestively associated with FA and demonstrated genetic differences across phenotypes. It highlights the need for a unified FA definition and sheds light on FA's shared genetic architecture with allergies.