Ecogenomics of respiratory diseases of public health significance

Abstract

Gene-environment interactions are the indisputable cause of most respiratory diseases. However, we still have very limited understanding of the mechanisms that guide these interactions. Although the conceptual approaches to environmental genomics were established several decades ago, the tools are only now available to better define the mechanisms that underlie the interactions among these important etiological features of lung disease. In this article, we summarize recent insights in the environmental genomics (ecogenomics) of common nonmalignant respiratory diseases (asthma, COPD, pulmonary fibrosis, and respiratory infections), describe the framework of gene-environment interactions that inform the pathogenesis of respiratory diseases, and propose future research directions that will help translate scientific advances into public health gains.

Figure 1

Gene-environment interaction complexity in the pathogenesis of respiratory diseases. Environmental exposures are the triggers that induce an individual response, based on genetic susceptibility factors. Coexposures and exposure characteristics modify the nature of the trigger, but environmental factors can also affect the genetic susceptibility through epigenetic mechanisms. Genetic susceptibility factors are the main determinants of the host response to an environmental trigger. Several genetic factors may be mutually interacting (epistasis), and gene expression can also be affected by environment–induced epigenetics. Nongenetic covariants may also alter the ultimate disease phenotype (outcome). Several clinically similar disease phenotypes may be included in a disease syndrome, which constitutes the final diagnosis.