Polygenic score for blood immunoglobulin E levels in adults explains food allergy risk in children 2615

Abstract Description Family history is a risk factor for food allergies (FA). This study aimed to assess the influence of genetic predisposition on immunoglobulin E (IgE) production as a predictive factor for susceptibility to FA in children. We developed novel models for calculating polygenic scores (PGS) associated with serum IgE levels and validated these models using data from Japanese adults (n = 66,946). Additionally, we evaluated the prevalence of FA across the PGS quintiles over approximately two years using data from Japanese children (n = 17,154). Here, PGS was significantly correlated with total IgE levels (Spearman’s ρ ≥ 0.174) and associated with an increased risk of FA (Benjamini–Hochberg q < 0.05). The direction of the risk association with PGS was similar to that of the HLA allele types. Children in the highest PGS quintile (Q5) exhibited a significantly elevated incidence risk ratio for FA (1.51-fold; 95% confidence interval; 1.30–1.76) compared to the low-to-middle quintiles (Q1–3). Egg white was the most prevalent allergen in children, and its prevalence increased significantly with elevated PGS levels. These results suggest that genetic predisposition to increased IgE levels in adults is associated with the development of FA during childhood, indicating that its influence throughout life is an immunological risk factor. Funding Sources Japan Agency for Medical Research and Development (AMED) JP23tm0124006; Japan Society for the Promotion of Science (JSPS) KAKENHI grant JP23K09747 Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)