Considerations in the search for epistasis
Marleen Balvert, Johnathan Cooper‐Knock, Julian Stamp, Ross P. Byrne, Soufiane Mourragui, Juami H. M. van Gils, Stefania Benónísdóttir, Johannes Schlüter, Kevin P. Kenna, Sanne Abeln, Alfredo Iacoangeli, Joséphine T. Daub, Brian L. Browning, Gizem Taş, Jiajing Hu, Yan Wang, Elham Alhathli, Calum Harvey, Luna Pianesi, Sara C. Schulte, Jorge González-Domínguez, Erik Garrisson, Lorentz workshop on epistasis, Ammar Al‐Chalabi, Jorge Avila Cartes, Jasmijn A. Baaijens, Joanna von Berg, Davide Bolognini, Paola Bonizzoni, Andrea Guarracino, Mehmet Koyutürk, Magda Markowska, Raghuram Dandinasivara, Jasper van Bemmelen, Sebastian Vorbrugg, Sai Zhang, Bogdan Pasanuic, M Snyder, Alexander Schönhuth, Letitia M.F. Sng, Natalie A. Twine
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.