The genetic epistasis effect has been widely acknowledged as an essential contributor to genetic variation in complex diseases. In this chapter, we introduce a powerful and efficient statistical method, called W-test, for genetic epistasis testing. A wtest R package is developed for the implementation of the W-test method, which provides various functions to measure the main effect, pairwise interaction, higher-order interaction, and cis-regulation of SNP-CpG pairs in genetic and epigenetic data. It allows flexible stagewise and exhaustive association testing as well as diagnostic checking on the probability distributions in a user-friendly interface. The wtest package is available in CRAN at https://CRAN.R-project.org/package=wtest .