Practice of Epidemiology Gene-Environment Interaction in Genome-Wide Association Studies

It is a commonly held belief that most complex diseases (e.g., diabetes, asthma, cancer) are affected in part by interactions between genes and environmental factors. However, investigators conducting genome-wide associ-ation studies typically test for only the marginal effects of each genetic marker on disease. In this paper, the authors propose an efficient and easily implemented 2-step analysis of genome-wide association study data aimed at identifying genes involved in a gene-environment interaction. The procedure complements screening for marginal genetic effects and thus has the potential to uncover new genetic signals that have not been identified previously. association; environment; genes; genetic markers; genetics; genome Abbreviations: E, environment; G, gene; GWAS, genome-wide association study; OR, odds ratio; SNP, single nucleotide polymorphism. Editor’s note: Two invited commentaries on this article appear on pages 227 and 231, and the authors ’ response is published on page 234. Many common, complex traits are believed to be a result of the combined effect of genes, environmental factors, and their interactions. For example, Ito et al. (1) showed a sig