Rethinking genetic models of asthma: the role of environmental modifiers

Asthma is a common, chronic disease with a complex etiology. To date, more than 35 genes have been associated with asthma or related phenotypes in multiple populations, but none of them has been shown to contribute to risk in all populations studied. We suggest that genetic susceptibility is both context dependent and developmentally regulated, and that ignoring the environmental context will miss many important associations and clues to pathogenesis. We define ‘environment’ broadly to include the in utero environment, maternal affection status and sex, and propose that epigenetic mechanisms are the link between our genes and our environment.