Longitudinal evidence on the relation between dietary intake of -3 (ω-3) very-long-chain polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mid-childhood and asthma risk is scarce. We aimed to investigate whether a higher intake of EPA and DHA from fish in childhood is associated with a lower risk of incident asthma.In the Avon Longitudinal Study of Parents and Children, dietary intakes of EPA and DHA from fish were estimated by food frequency questionnaire at 7 years of age. We used logistic regression, controlling for confounders, to analyse associations between intake of EPA and DHA (quartiles) and incidence of doctor-diagnosed asthma at age 11 or 14 years, and explored potential effect modification by a fatty acid desaturase ( ) polymorphism (rs1535). Replication was sought in the Swedish BAMSE birth cohort.There was no evidence of association between intake of EPA plus DHA from fish and incident asthma overall (n=4543). However, when stratified by genotype, the odds ratio comparing the top bottom quartile among the 2025 minor G allele carriers was 0.49 (95% CI 0.31-0.79; p =0.006), but no inverse association was observed in the homozygous major A allele group (OR 1.43, 95% CI 0.83-2.46; p =0.19) (p =0.006). This gene-nutrient interaction on incident asthma was replicated in BAMSE.In children with a common variant, higher intake of EPA and DHA from fish in childhood was strongly associated with a lower risk of incident asthma up to mid-adolescence.