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Objectives: Anxiety sensitivity (AS) has predictive potential for the development of anxiety disorders. We investigated the role that gene–environment (G × E) interactions, focussing on childhood trauma (CT) and selectedSLC6A4variants, play in modulating levels of AS in a South African adolescent population.Methods: All adolescents (n = 951) completed measures for AS and CT. SixSLC6A4polymorphisms were genotyped. G × E influences on AS levels were assessed using multiple linear regression models. Relevant confounders were included in all analyses.Results: Xhosa (n = 634) and Coloured (n = 317) participants were analysed independently of one another. The5-HTTLPR-rs25531L-Ghaplotype associated with reduced AS among Xhosa adolescents (P = 0.010). In addition, the rs1042173CC-genotype protected against increased levels of AS in Xhosa participants who had experienced increased levels of CT (P = 0.038). Coloured males homozygous for theS-allele had significantly increased levels of AS compared to Coloured males with at least oneL-allele (P = 0.016).Conclusions: This is the first study to be conducted on AS in adolescents from two ethnically diverse populations. Results indicate that theL-Ghaplotype confers protection against high AS levels in a Xhosa population. Furthermore, increased CT was found to protect against high levels of AS in Xhosa rs1042173CC-carriers. [ABSTRACT FROM PUBLISHER]