Here we propose an easy-to-implement joint location-scale (JLS) testing framework that simultaneously tests the null hypothesis of equal mean and equal variance between genotypes, by aggregating association evidence from the individual location-only and scale-only tests, focusing on Fisher’s method of combining information (JLS-Fisher). The proposed method detects association in the presence of underlying genetic main and/or interaction effects, without specifying the interactors; it allows any type of individual location and scale tests to be combined, making it particularly useful for gene-based, gene-set, and pathway analyses.