Detecting epistasis using mouse chromosomal substitution strains
Complex trait regulation by additive and non-additive effects is unclear and often ignored in genome-wide association studies. Mouse chromosome substitution strains using A/J-derived substituted chromosomes 4 and 6 are a powerful model to detect additive and epistatic loci for hepatic-related traits and gene expression. We identified and mapped 768 additive and 519 epistatic QTLs regulating expression and additive QTLs for fat pad weight, platelets, and granulocyte percentage and epistatic QTLs for lymphocyte percentage and red cell distribution width. The variance attributed to epistatic and additive QTLs were about equal, demonstrating the importance of accounting for epistasis in association studies.