BackgroundLittle is known about the genetics of food allergy (FA) to various allergens and the heterogeneity of FA in adults.ObjectiveWe aimed to investigate genetic susceptibility to FA in an adult population and to assess the association between secondary FA and allergic rhinitis (AR).MethodsFA and allergen‐specific FA were defined based on in‐depth questionnaires and a previously published FA algorithm in the Lifelines. We performed a series of genome‐wide association studies (GWAS) on FA and nine allergen‐specific (e.g., hazelnut) FA in 21,353 adults in Lifelines. Single nucleotide polymorphisms (SNPs) (p < 1E‐5) were replicated in a second independent set of 15,518 adults participating in the Lifelines followed by meta‐analysis of the results of the two datasets. We subsequently investigated the causal relationship of AR to FA using Mendelian randomization (MR) analysis.ResultsWe observed co‐occurrence of tree nuts and apple FA, with over 80% of this group also reporting AR. After meta‐analysis, we identified one genome‐wide significant locus near HLA‐DPA1 associated with self‐reported hazelnut allergy (hazelnutFA), of which the top SNP is rs5025825 (p = 2.51E‐9, OR = 1.43). Two‐sample MR indicated that AR is a significant causal risk factor for hazelnutFA (p‐IVW = 5.27E‐10, β = 5.90, p‐pleiotropy = 0.46).ConclusionOur questionnaire enabled a large GWAS on self‐reported FA in Dutch adults. We report one novel locus in the human leukocyte antigens (HLA) region associated with hazelnutFA, implying an association with antigen recognition. Our findings genetically link secondary FA to AR in adults.

中文翻译：

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全基因组关联研究揭示了过敏性鼻炎和榛子过敏之间的因果关系


背景对各种过敏原的食物过敏 （FA） 的遗传学和成人 FA 的异质性知之甚少。目的我们旨在调查成人人群对 FA 的遗传易感性，并评估继发性 FA 与过敏性鼻炎 （AR） 之间的关联。方法FA 和过敏原特异性 FA 是根据深入的问卷和先前在 Lifelines 中发表的 FA 算法定义的。我们在 Lifelines 的 21,353 名成年人中对 FA 和 9 种过敏原特异性（例如榛子）FA 进行了一系列全基因组关联研究 （GWAS）。单核苷酸多态性 （SNP） （p < 1E-5） 在参与 Lifelines 的 15,518 名成年人的第二组独立组中复制，然后对两个数据集的结果进行荟萃分析。随后，我们使用孟德尔随机化 （MR） 分析研究了 AR 与 FA 的因果关系。结果我们观察到坚果和苹果 FA 同时发生，该组中超过 80% 的人还报告了 AR。经过荟萃分析，我们确定了 HLA-DPA1 附近一个与自我报告的榛子过敏 （hazelnutFA） 相关的全基因组重要位点，其中前 SNP 是 rs5025825 （p = 2.51E-9，或 = 1.43）。双样本 MR 表明 AR 是榛子 FA 的重要致病危险因素 （p-IVW = 5.27E-10，β = 5.90，p-多效性 = 0.46）。结论我们的问卷对荷兰成年人自我报告的 FA 进行了大量 GWAS。我们报道了人类白细胞抗原 （HLA） 区域中的一个与 hazelnutFA 相关的新位点，这意味着与抗原识别有关。我们的研究结果将继发性 FA 与成人的 AR 遗传相关。