For many traits, causal loci uncovered by genetic mapping studies explain only a minority of the heritable contribution to trait variation. Multiple explanations for this missing heritability have been proposed. Single nucleotide polymorphism (SNP)-SNP interaction (epistasis), as one of the compelling models, has been widely studied. However, the genome-wide scan of epistasis, especially for quantitative traits, poses huge computational challenges. Moreover, covariate adjustment is largely ignored in epistasis analysis due to the massive extra computational undertaking.