This study describes the role of two STAT6 gene variants in food allergy using data of patients and their parents who underwent double-blind placebo-controlled food challenges (DBPCFCs). After quality control, 369 trios were analyzed including 262 children (71.0%) with food allergy. Associations were tested by family based association testing (FBAT). The A alleles of both SNPs were associated with food allergy (p=0.036 and p=0.013 for rs324015 and rs1059513, respectively). Furthermore, these A alleles were associated with peanut allergy, higher sIgE levels to both peanut and cow's milk, more severe symptoms and higher eliciting doses during peanut and cow's milk DBPCFCs (all p<0.05). In silico analysis indicates that the identified risk variants increase STAT6 expression which stimulates the differentiation of CD4+ T cells to the Th2 subset. In conclusion, STAT6 variants may be involved in the pathophysiology of food allergy and their role seems to be independent of the allergenic food. This article is protected by copyright. All rights reserved.