Gene-environment interactions in the development of asthma and atopy.

Asthma is a complex multifactorial disorder involving a variety of different mechanisms. Little has changed in asthma treatment over the past five decades. There is evidence for a strong genetic component of asthma, but genetic studies have produced heterogeneous results with little replication, with most of the heritability remaining unexplained. The rapid increase in asthma prevalence over a short time period suggests that environmental exposures play an important role, but there is a considerable heterogeneity in the results describing the effect of different environmental exposures. There are many reasons for the lack of replication in genetic association studies and those of environmental exposures. These include the failure to consider that asthma may arise as a consequence of environmental factors, modulating the risk in genetically susceptible individuals via gene-environment interactions. In addition, many studies rely on oversimplified phenotypes often derived through aggregation of several heterogeneous conditions (e.g., 'physician-diagnosed asthma').