 Our study identified 44 independent genetic variants associated with early onset persistent, 25 with preschool remitting, 33 with mid-childhood remitting, and 32 with late onset wheeze. We also found a novel locus on chromosome 9Q21.13, near-ansion 1, AnxA1, associated exclusively with early onset persistent wheeze. This locus contains a single nucleotide polymorphism, SNP, called RS75260654, which is associated with reduced levels of AnxA1 protein and mRNA in lung tissue after exposure to house dust mite, HDM. In addition, we found that AnxA1 deficient mice have enhanced airway hyperreactivity and TH2 inflammation when exposed to HDM. These findings suggest that targeting this pathway could be a promising therapeutic option for persistent asthma.