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Asthma is a heterogeneous disease, consisting of varying phenotypes affected by different genetic, epigenetic, clinical and environmental factors. We aimed to assess whether eosinophilia modified the effect of genetic variants on exacerbation risk in adults with asthma. Within the UK Biobank study, individuals with asthma were identified using self-reported data, hospitalization data and General Practitioners (GP) records. Exacerbations were identified as either asthma–related hospitalization, GP record of asthma exacerbation, or an Oral Corticosteroid (OCS) burst prescription. An interaction analysis was used to assess whether eosinophilia (defined as a blood eosinophil level ≥300 cells/μl) modifies the effect of genetic variants on asthma exacerbation risk using an interaction term (SNP*eosinophilia) in a logistic regression model adjusted for age, sex, smoking status, and eosinophilia. We identified 11,604 individuals with asthma with at least one exacerbation (cases), and 37,890 individuals with asthma with no recorded exacerbations (controls). Interaction analyses identified 14 SNPs in linkage disequilibrium on chromosome 18 affecting exacerbation risk in eosinophilic patients (OR:1.11;P<5x10-7 for 14 SNPs interaction tests). These SNPs were associated with CXADRP3, an adenovirus receptor pseudogene. Eosinophilia may modify the effect of genetic variants on the risk of asthma exacerbations. Further research and replication of these findings may be needed to ascertain genetic variants’ role in the development and severity of different phenotypes within asthma.