Baud, AmelieCasale, Francesco PaoloBarkley-Levenson, Amanda M.Farhadi, NilgounMontillot, CharlotteYalcin, BinnazNicod, JeromePalmer, Abraham A.Stegle, Oliver2022-05-162022-05-162021Baud A, Casale FP, Barkley-Levenson A, Farhadi N, Montillot C, Yalcin B et al. Dissecting indirect genetic effects from peers in laboratory mice. Genome Biol. 2021 Jul 26;22(1):216. DOI: 10.1186/s13059-021-02415-x1474-7596http://hdl.handle.net/10230/53089Background: The phenotype of an individual can be affected not only by the individual's own genotypes, known as direct genetic effects (DGE), but also by genotypes of interacting partners, indirect genetic effects (IGE). IGE have been detected using polygenic models in multiple species, including laboratory mice and humans. However, the underlying mechanisms remain largely unknown. Genome-wide association studies of IGE (igeGWAS) can point to IGE genes, but have not yet been applied to non-familial IGE arising from "peers" and affecting biomedical phenotypes. In addition, the extent to which igeGWAS will identify loci not identified by dgeGWAS remains an open question. Finally, findings from igeGWAS have not been confirmed by experimental manipulation. Results: We leverage a dataset of 170 behavioral, physiological, and morphological phenotypes measured in 1812 genetically heterogeneous laboratory mice to study IGE arising between same-sex, adult, unrelated mice housed in the same cage. We develop and apply methods for igeGWAS in this context and identify 24 significant IGE loci for 17 phenotypes (FDR < 10%). We observe no overlap between IGE loci and DGE loci for the same phenotype, which is consistent with the moderate genetic correlations between DGE and IGE for the same phenotype estimated using polygenic models. Finally, we fine-map seven significant IGE loci to individual genes and find supportive evidence in an experiment with a knockout model that Epha4 gives rise to IGE on stress-coping strategy and wound healing. Conclusions: Our results demonstrate the potential for igeGWAS to identify IGE genes and shed light into the mechanisms of peer influence.application/pdfeng© Amelie Baud et al. 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were madeGenèticaGenòmicaGenotipFenotipinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s13059-021-02415-xinfo:eu-repo/semantics/openAccess