A quantitative genetic analysis of intermediate asthma phenotypes

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). 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. 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 (rho(A)) = 0.37, whereas the strongest environmental resemblance was observed between airway responsiveness and airway obstruction, specific environmental correlation (rho(E)) = -0.46, and between FeNO and airway responsiveness, rho(E) = 0.34. Asthma is a complex disease characterized by a set of etiologically heterogeneous biomarkers, which likely constitute diverse targets of intervention.