Selection of genes for gene-environment interaction studies: a candidate pathway-based strategy using asthma as an example

BACKGROUND: The identification of gene by environment (GxE) interactions has emerged as a challenging but essential task to fully understand the complex mechanism underlying multifactorial diseases. Until now, GxE interactions have been investigated by candidate approaches examining a small number of genes, or agnostically at the genome wide level. PRESENTATION OF THE HYPOTHESIS: In this paper, we propose a gene selection strategy for investigation of gene-environment interactions. This strategy integrates the information on biological processes shared by genes, the canonical pathways to which they belong and the biological knowledge related to the environment in the gene selection process. It relies on both bioinformatics resources and biological expertise. TESTING THE HYPOTHESIS: We illustrate our strategy by considering asthma, tobacco smoke as the environmental exposure, and genes sharing the same biological function of “response to oxidative stress”. Our filtering strategy leads to a list of 28 pathways involving 182 genes for further GxE investigation. IMPLICATIONS OF THE HYPOTHESIS: By integrating the environment into the gene selection process, we expect that our strategy will improve the ability to identify the joint effects and interactions of environmental and genetic factors in disease.