genes; http://atgu.mgh.harvard.edu/inrich/; Lee et al., 2012), to name a few. It is important to note however that pathway approaches are limited to existing knowledge about a gene and the biological pathways relevant to the disease. Furthermore, study results may not be generalizable because the approach assumes that genes influence the disease/trait through a common biological pathway, which in the case of addiction phenotypes is only partially true (Palmer et al., 2012). Genomewide epistatic modeling (GEM) approaches provide a means to model biological interactions while also utilizing the clustering approach used in pathway/gene-set analyses.
