Balvert, MarleenCooper-Knock, JohnathanStamp, JulianByrne, Ross P.Mourragui, Soufianevan Gils, JuamiBenonisdottir, StefaniaSchlüter, JohannesKenna, KevinGonzález-Domínguez, Jorge2026-07-232026-07-232024Balvert, M., Cooper-Knock, J., Stamp, J. et al. Considerations in the search for epistasis. Genome Biol 25, 296 (2024). https://doi.org/10.1186/s13059-024-03427-z1474-760Xhttps://hdl.handle.net/2183/48927The code for the simulated data is available at Github and Zenodo under an MIT license. - Balvert M, Cooper-Knock J, Stamp J, Byrne RP, Mourragui S, van Gils J et al. Population structure confounds regression-based epistasis detection. 2024. Github https://github.com/jdstamp/leiden_paper. - Balvert M, Cooper-Knock J, Stamp J, Byrne RP, Mourragui S, van Gils J, et al. Population structure confounds regression-based epistasis detection. 2024. Zenodo. https://doi.org/10.5281/zenodo.13940750. A Correction to this paper has been published: https://doi.org/10.1186/s13059-025-03477-x (20 January 2025)[Abstract]: Epistasis refers to changes in the effect on phenotype of a unit of genetic information, such as a single nucleotide polymorphism or a gene, dependent on the context of other genetic units. Such interactions are both biologically plausible and good candidates to explain observations which are not fully explained by an additive heritability model. However, the search for epistasis has so far largely failed to recover this missing heritability. We identify key challenges and propose that future works need to leverage idealized systems, known biology and even previously identified epistatic interactions, in order to guide the search for new interactions.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/EpistasisGenetic InteractionGenetics ResearchGenetic LinkageGenetics and GenomicsGenetics Epistatic Interactions in Fitness Landscapesjournal articleopen access10.1186/s13059-024-03427-z