Background Although the development of allergic rhinitis (AR) is associated with multiple genetic and hygienic environmental factors, previous studies have focused mostly on the effect of a single factor on the development of AR. This study aimed to investigate the combined effect of multiple genetic and hygienic environmental risk factors on AR development in school children. Methods We conducted a cross-sectional study, comprising 1,797 children aged 9–12 years. Weighted environmental risk score (ERS) was calculated by using four hygienic environmental factors, including antibiotic use during infancy, cesarean section delivery, breast milk feeding, and having older siblings. Weighted polygenic risk score (PRS) was calculated by using four single nucleotide polymorphisms (SNPs), including interleukin-13 (rs20541), cluster of differentiation 14 (rs2569190), toll-like receptor 4 (rs1927911), and glutathione S-transferase P1 (rs1695). Multivariable logistic regression analysis was used. Results More than three courses of antibiotic use during infancy increased the risk of current AR (adjusted odd ratio [aOR], 2.058; 95% confidence interval [CI]: 1.290–3.284). Having older siblings, especially >2 (aOR, 0.526; 95% Cl: 0.303–0.913) had a protective effect. High ERS (>median; aOR, 2.079; 95% Cl: 1.466–2.947) and PRS (>median; aOR, 1.627; 95% Cl: 1.117–2.370) increased the risk of current AR independently. Furthermore, children who had both high ERS and PRS showed a higher risk of current AR (aOR, 3.176; 95% Cl: 1.787–5.645). Conclusions Exposure to multiple hygienic risk factors during early life increases the risk of AR in genetically susceptible children. Key words: Allergic rhinitis, Hygiene, Genes, Risk factors, Child, Gene-environment interaction, Anti-bacterial agent

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