AIM: To study the relative contribution of genetic and environmental factors to the correlation between exhaled nitric oxide (FeNO), airway responsiveness, airway obstruction, and serum total immunoglobulin E (IgE). METHODS: Within a sampling frame of 21,162 twin subjects, 20-49 years of age, from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins) who either themselves and/or their co-twins reported a history of asthma at a nationwide questionnaire survey, were clinically examined. Traits were measured using standard techniques. Latent factor models were fitted to the observed data using maximum likelihood methods. RESULTS: Additive genetic factors explained 67% of the variation in FeNO, 43% in airway responsiveness, 22% in airway obstruction, and 81% in serum total IgE. In general, traits had genetically and environmentally distinct variance structures. The most substantial genetic similarity was observed between FeNO and serum total IgE, genetic correlation (rhoA) = 0.37, whereas the strongest environmental resemblance was observed between airway responsiveness and airway obstruction, specific environmental correlation (rhoE) = -0.46, and between FeNO and airway responsiveness, rhoE = 0.34. CONCLUSIONS: Asthma is a complex disease characterized by a set of etiologically heterogeneous biomarkers, which likely constitute diverse targets of intervention.