The study of gene-environment (GxE) interactions in complex diseases has a long history [Haldane 1938; Khoury, et al. 1988; Thomas 2000]. In contrast to simple Mendelian disorders, susceptibility to common complex traits, including cancer, is multi-factorial, involving multiple genetic and environmental risk factors. Over the past decade, the field has progressed from candidate gene and candidate gene-gene (GxG) and GxE interaction studies to genome-wide association studies (GWAS) and gene-environment-wide interaction studies (GEWIS [Khoury and Wacholder 2009] or “GE-Whiz” [Thomas, et al. 2012]). Using the Human Genome Epidemiology (HuGE) Navigator tool [Yu, et al. 2008] to track publications, Dr. Khoury and colleagues identified exponential increases in published genetic epidemiology literature from 2001 to 2010, including GWAS, substantive epidemiologic studies, method analyses, meta-analyses, and reviews [Khoury, et al. 2011]. They noted challenges in developing and applying appropriate methods for analysis and synthesis of GxE interactions. These challenges stem from the complex, evolving, and expanding nature of genetic and environmental data collected. The field continues to face new challenges as we move into the “Post-GWAS” era [Aschard, et al. 2012; Dempfle, et al. 2008; Khoury, et al. 2011; Liu, et al. 2012; Thomas 2010].
