Genetic and environmental influences on objective intermediate asthma phenotypes in Dutch twins.

ABSTRACT

It is unclear to what extent the same set of environmental or genetic factors regulate objective intermediate asthma phenotypes. We examined heritabilities of these phenotypes and estimated their environmental and genetic overlap. We studied baseline lung function (forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC), bronchial hyperresponsiveness, number of positive skin prick tests (SPT) to 11 allergens, serum total immunoglobulin (Ig)E, number of positive specific IgE tests to four allergens and eosinophil counts. 103 twin pairs were studied (46 monozygotic and 57 dizygotic; mean age 22.5 yrs, range 17.0-27.0 yrs). Univariate and bivariate genetic analyses were performed after adjustment for significant covariates. All intermediate asthma phenotypes showed significant heritabilities (47-83%). Most phenotypes were substantially correlated, which was mainly due to shared genetic factors. Pairs of phenotypes with the largest genetic correlations were specific IgE and SPT (0.98), and total IgE with specific IgE (0.87), with SPT (0.72), and with eosinophils (0.62). SPT showed significant environmental correlations with total IgE (0.65), specific IgE (0.70) and bronchial hyperresponsiveness (0.44). Genetic effects explain the majority of the variation in objective intermediate asthma phenotypes. Additionally, correlations between pairs of these traits are also mainly explained by genetic rather than environmental factors.